Ranking
Safest Painkillers and Pain Relievers 2026
Every medicine we score whose main licensed use is relieving pain, from paracetamol and ibuprofen to prescription opioids. Each score rates the medicine as prescribed or as the pack directs, for an average adult, on serious side effects, overdose margin, interactions, dependence, regulatory warnings and track record. The right painkiller for you depends on your health, your other medicines, your age and whether you are pregnant.
Updated · Scores update with each page
The ranking
Acetaminophen (paracetamol)
At the doses on the box, acetaminophen (paracetamol, Tylenol) is one of the gentlest painkillers there is. The risk is the small gap to a liver-damaging dose, which people cross by accident when they combine products.
Score 77, grade BCelecoxib
Celecoxib (Celebrex) is a prescription anti-inflammatory that causes fewer stomach ulcers and bleeds than older NSAIDs. In the PRECISION trial its heart risk at 100 mg twice a day was no worse than ibuprofen or naproxen, but higher doses raised heart attacks in an earlier trial.
Score 74, grade BIbuprofen
For a few days at the dose on the pack, ibuprofen (Advil, Motrin, Nurofen) is a safe choice for most adults. The risks build with dose and time, mainly stomach bleeding, kidney strain and a small rise in heart attack and stroke.
Score 74, grade BMeloxicam
Meloxicam (Mobic) is a once-a-day prescription NSAID for arthritis. Its heart risk in population studies looks similar to ibuprofen and celecoxib, but its stomach bleeding risk is closer to diclofenac, and its long half-life means each dose stays in the body for a day.
Score 73, grade BNaproxen
Naproxen (Aleve, Naprosyn) is a safe short-term painkiller for most adults at the dose on the pack. Its heart risk looks lower than other NSAIDs in trials, but stomach bleeding, kidney strain and interactions build up with dose, age and time.
Score 73, grade BDiclofenac
Diclofenac (Voltaren, Voltarol) is an NSAID painkiller sold as tablets, injections and a skin gel. The gel puts little of the drug into the blood and suits knee or hand arthritis. Tablets work well but raise heart attack and stroke risk more than ibuprofen or naproxen, and can harm the liver.
Score 69, grade CKetoprofen
Ketoprofen is an NSAID sold as capsules (Orudis in the US) and, across Europe and the UK, mainly as a skin gel. The gel relieves knee arthritis pain with little drug reaching the blood, but it can cause allergic rashes in sunlight. Taken by mouth, it is one of the harder NSAIDs on the stomach.
Score 69, grade CAspirin
Aspirin is two medicines in one. Low-dose aspirin after a heart attack or stroke has a clear benefit, while daily use by healthy older people mostly adds bleeding risk. At pain-relief doses it carries stomach bleeding and overdose risks, and children should not take it.
Score 68, grade CEtoricoxib
Etoricoxib (Arcoxia) is a COX-2 inhibitor sold in the UK and much of the world, but never approved in the US. In a 34,701-patient programme its heart risk matched high-dose diclofenac with fewer stomach problems, but it raises blood pressure more than most painkillers.
Score 67, grade CMetamizole (dipyrone)
Metamizole (dipyrone; Novalgin, Nolotil, Analgin) treats severe pain and fever in much of Europe and Latin America. It is not an NSAID, but it can wipe out white blood cells without warning, which is why the US withdrew it in 1977 and the EU strengthened its warnings in 2024.
Score 66, grade CCodeine
Codeine (Tylenol with Codeine, co-codamol) is a weak opioid that works only once the liver turns it into morphine. That varies with the CYP2D6 gene, so it can be useless for some people and life-threatening for others. It is addictive, banned for children under 12 in the US and often combined with acetaminophen.
Score 40, grade DDihydrocodeine
Dihydrocodeine (co-dydramol, first sold as DF118) is a codeine-like opioid used mostly in the UK and Europe for moderate pain. It carries the usual opioid risks of addiction and slowed breathing, and it is often sold with paracetamol, so an overdose can also damage the liver.
Score 38, grade FTramadol
Tramadol (Ultram, Ultracet, ConZip) is often seen as a mild painkiller, but it is an opioid with the same boxed warning as stronger ones, plus seizures, serotonin syndrome and low blood sodium or sugar. How much active drug a person makes depends on the CYP2D6 gene and other medicines they take.
Score 34, grade FTapentadol
Tapentadol (Nucynta, Palexia) is a strong opioid painkiller that also works on noradrenaline, like a cousin of tramadol. It causes less constipation than oxycodone and turns up less in misuse data, but it carries the full opioid boxed warning and adds seizure and serotonin syndrome risks.
Score 32, grade FHydrocodone
Hydrocodone, mostly prescribed with acetaminophen (Vicodin, Norco and generics), relieves short-term pain but carries every risk of a strong opioid. Addiction can develop at prescribed doses, mixing it with alcohol or benzodiazepines can stop breathing, and the acetaminophen inside can damage the liver.
Score 27, grade FMorphine
Morphine (MS Contin, generic tablets, oral solution and injection) is the opioid every other one is measured against, and it relieves severe pain well. It carries the full set of strong-opioid risks, including addiction at prescribed doses, fatal slowed breathing and dangerous mixes with alcohol or benzodiazepines.
Score 27, grade FHydromorphone
Hydromorphone (Dilaudid) is a strong opioid used for severe pain in hospital, cancer care and after surgery. It works like morphine at a fraction of the dose, which makes mix-ups with morphine and concentrated liquids or injections a specific danger, on top of addiction and fatal slowed breathing.
Score 26, grade FOxycodone
Oxycodone (OxyContin, Percocet, Roxicodone, OxyNorm) controls severe pain well but carries the risks of every strong opioid. Addiction can develop even in people who take it as prescribed, and an overdose, or a mix with alcohol or benzodiazepines, can stop breathing.
Score 26, grade FOxymorphone
Oxymorphone (once sold as Opana and Opana ER) is a strong US opioid for severe pain, now sold only as generic tablets. It has the risks of oxycodone at half the dose, plus unusual sensitivity to alcohol, food and liver disease. Opana ER was withdrawn in 2017 at the FDA's request because of injection abuse.
Score 24, grade FFentanyl
Prescription fentanyl, mainly patches and hospital injections, controls severe pain in people already used to strong opioids. A patch on an opioid-naive person, heat on the skin or a used patch found by a child can cause a fatal overdose. Illicit fentanyl is a separate problem.
Score 22, grade F
Which medicines are on this list
The rule is the main licensed use. A medicine is here when relieving pain is what it is mainly approved for. That covers the Over-the-counterA medicine you can buy without a prescription, in a pharmacy or shop, with directions on the pack for safe use without a doctor.More in the glossary painkillers, acetaminophen (paracetamol), ibuprofen, naproxen and aspirin; the prescription anti-inflammatories meloxicam, diclofenac, whose gel is also sold over the counter, ketoprofen, scored as the US capsules, and the coxibs celecoxib and etoricoxib, which is sold in the UK but not in the US; metamizole, a painkiller widely used in Europe and Latin America that the US withdrew in 1977; and the opioids prescribed for pain, from codeine, dihydrocodeine, tramadol and tapentadol to hydrocodone, oxycodone, morphine, hydromorphone, oxymorphone and fentanyl.
Some medicines we score that also treat pain are left out. Buprenorphine and methadone are opioids whose main use is treating opioid addiction. Gabapentin and pregabalin are licensed for nerve pain and seizures, not for everyday pain. Duloxetine is an antidepressant that is also approved for some kinds of chronic pain, amitriptyline is an antidepressant that the UK also licenses for nerve pain and migraine prevention, and nortriptyline, its close relative, is licensed only for depression, though UK doctors often prescribe it for nerve pain. All three are on our antidepressant list.
How the order is built
Each medicine is scored on six factors. Serious side effects at normal doses count for 30%, the Overdose marginHow far a normal dose is from a harmful one. A wide margin means an accidental extra dose is unlikely to cause serious harm.More in the glossary for 20%, interactions and dependence for 15% each, and regulatory warnings and track record for 10% each. We score each drug as labelled, at the dose on the pack or the prescription; misuse is described on each page but does not set the score. The rubrics are on how we score medications.
The list is those scores sorted from the highest down, so it moves when we update a page after a new warning or study. That is why this text does not quote scores.
The non-opioid painkillers sit at the top
Paracetamol and the NSAIDs have opposite weak points. Paracetamol does not irritate the stomach, does not thin the blood and is not addictive, but liver damage can start not far above the 4,000 mg daily limit, and it causes about half of acute liver failure in the US. Ibuprofen and naproxen are hard to overdose on, but every prescription NSAID label in the US carries a Boxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary for heart attack, stroke and stomach bleeding, which grow with dose and time. Meloxicam lasts a whole day on one dose, and in population studies its stomach risk was close to diclofenac's. Ketoprofen capsules were harder on the stomach than ibuprofen in the same studies; its gel puts little of the drug into the blood but can cause a rash in sunlight. Celecoxib is easier on the stomach than the older NSAIDs, with a similar heart risk at modest doses. Etoricoxib, the other coxib, also spares the stomach but raises blood pressure more than most painkillers, and the FDA turned it down in 2007. Diclofenac tablets raise heart risk more than ibuprofen or naproxen and can harm the liver, while diclofenac gel puts far less of the drug into the blood. Aspirin raises bleeding risk even at low doses and has a narrower Overdose marginHow far a normal dose is from a harmful one. A wide margin means an accidental extra dose is unlikely to cause serious harm.More in the glossary. Metamizole can cause a rare collapse in white blood cells, fatal in about 16% of the cases reported in the EU.
Why the opioids are near the bottom
All ten opioids carry the full US opioid Boxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary. In FDA-required studies of people on long-term opioids, about 1% to 6% developed addiction within a year, and slowed breathing can kill, most often at the start, after a dose increase or with alcohol or sedatives. Codeine and tramadol are weaker but less predictable, and tapentadol adds seizure and Serotonin syndromeA reaction caused by too much serotonin in the body, usually from combining medicines that raise it. Symptoms range from shivering to high fever.More in the glossary risks. Dihydrocodeine is about as strong as codeine, yet deaths mentioning it in England and Wales reached a record in 2024. Oxymorphone is about three times as strong as oral morphine, and alcohol, food and liver disease all raise the amount in the blood; its brand Opana ER was withdrawn in 2017 at the FDA's request. Hydromorphone is about five times as strong as oral morphine per milligram, so dose and name mix-ups are a particular danger, and fentanyl patches are only for people already used to strong opioids. A lower place does not make an opioid the wrong medicine: after major surgery or for severe pain it may be the right one, used for the shortest time your prescriber advises.
What the score does not tell you
The score rates each medicine for an average adult taking it as directed. It does not measure how well it relieves your pain, and it cannot weigh your stomach, kidneys, heart, liver, age, pregnancy or the other medicines you take. Do not start, stop or switch a painkiller on the strength of this list; ask your doctor or pharmacist. If you take opioids every day, talk to your prescriber before you stop, because stopping suddenly can cause severe withdrawal. If someone has taken too much of any painkiller, call Poison Control on 1-800-222-1222 in the US or NHS 111 in the UK, even if they seem well.
Questions
What is the safest painkiller?
There is no single answer, because the common painkillers fail in different ways. Paracetamol (acetaminophen) does not irritate the stomach, thin the blood or cause addiction, but the gap between the daily limit of 4,000 mg and a dose that harms the liver is small. Ibuprofen and naproxen are much harder to overdose on, but they can cause stomach bleeding, kidney strain and heart problems with longer use. A pharmacist can tell you which suits your health and your other medicines.
Which painkiller is safest for the stomach?
Paracetamol (acetaminophen) is the gentlest of the common painkillers on the stomach. NSAIDs such as ibuprofen, naproxen and aspirin can cause ulcers and bleeding, about 1% of people over 3 to 6 months of regular use and 2% to 4% over a year on the FDA label, and only about one in five has warning signs first. In a 2012 analysis of observational studies, celecoxib and ibuprofen had the lowest risk of serious stomach complications, and diclofenac, meloxicam, ketoprofen and naproxen about twice as much as ibuprofen. The coxibs celecoxib and etoricoxib cause fewer ulcers and bleeds than the older NSAIDs, but taking low-dose aspirin with them cancels much of that advantage. Opioids do not cause ulcers, but constipation is near universal. If you have had an ulcer or take a blood thinner, ask your doctor before taking any NSAID.
Which painkiller is safest for the kidneys?
Paracetamol (acetaminophen) at label doses is the usual choice, because it does not cut blood flow to the kidneys the way NSAIDs do. NSAIDs such as ibuprofen and naproxen reduce blood flow to the kidneys, which rarely matters in a healthy adult on a short course but can cause kidney injury in people who are older or dehydrated, or who take a diuretic with an ACE inhibitor or ARB. Morphine's active breakdown products build up in kidney failure. If you have kidney disease, ask your doctor which painkiller and dose to use.
Which painkiller is safest for the heart?
Paracetamol (acetaminophen) does not carry the heart warning that NSAIDs do. The FDA warns that all NSAIDs except aspirin raise the risk of heart attack and stroke, and that the risk can start in the first weeks. Naproxen has the best heart data of the NSAIDs in a large 2013 analysis of trials, but its US label keeps the same Boxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary. Diclofenac tablets carry the most heart risk of the common NSAIDs. At high doses that analysis put them level with the coxibs, and Europe has barred them for people with heart disease since 2013. Celecoxib at modest doses did no worse than ibuprofen or naproxen in the 2016 PRECISION trial. Etoricoxib, sold in the UK but not in the US, raises blood pressure more than most NSAIDs, and its UK label rules it out for people with heart disease or blood pressure that stays above 140/90 mmHg. If you have heart disease, high blood pressure or a past stroke, or take low-dose aspirin, ask your doctor before taking an NSAID.
Can I take ibuprofen and paracetamol together?
Yes, for most adults. They work in different ways and do not interact, so many people combine or alternate them for a short time. Each keeps its own daily limit, 4,000 mg for paracetamol and 1,200 mg for ibuprofen bought Over-the-counterA medicine you can buy without a prescription, in a pharmacy or shop, with directions on the pack for safe use without a doctor.More in the glossary, and paracetamol also hides in cold remedies and in prescription tablets such as Percocet and Norco. Do not combine ibuprofen with another NSAID such as naproxen or aspirin, and ask a pharmacist first if you have stomach, kidney or heart problems.
What is the safest opioid painkiller?
None of them is low-risk. Every opioid on this list carries a Boxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary on addiction, slowed breathing and dangerous mixes with alcohol or benzodiazepines. Codeine, dihydrocodeine and tramadol sit above the strong opioids. Codeine and tramadol depend on the CYP450 enzymesA family of liver enzymes that break down many medicines. When another drug or supplement speeds them up or slows them down, drug levels change.More in the glossary liver enzyme, so they can do little for some people and too much for others, and tramadol adds seizures and Serotonin syndromeA reaction caused by too much serotonin in the body, usually from combining medicines that raise it. Symptoms range from shivering to high fever.More in the glossary. Dihydrocodeine depends less on that enzyme, but it causes the same addiction and breathing risks. Tapentadol, a relative of tramadol, avoids the CYP2D6 problem but shares the seizure and serotonin risks and is controlled as tightly as oxycodone. The choice of opioid and dose belongs to your prescriber, and the labels ask them to discuss keeping naloxone at home.
Which painkillers are safe in pregnancy?
Paracetamol (acetaminophen) is still the painkiller most often recommended in pregnancy. In September 2025 the FDA began a label change about a possible link with autism and ADHD, while saying a causal link has not been shown. The FDA warns against NSAIDs such as ibuprofen and naproxen from about 20 weeks, the UK label rules out etoricoxib at any stage of pregnancy, metamizole must not be used in the last three months, and opioid labels warn of withdrawal symptoms in the newborn. Ask your midwife or doctor before taking any painkiller while pregnant.