TL;DR
- Paracetamol (acetaminophen) relieves pain and lowers fever. It does not treat inflammation. Safer on the stomach and kidneys, riskier on the liver in overdose or with chronic alcohol use.
- Ibuprofen relieves pain, lowers fever, and treats inflammation. More likely to cause GI erosions and bleeding, more strain on the kidneys, raises blood pressure, and a poor mix with anticoagulants.
- For uncomplicated fever in an adult or a child over 3 months old, international guidelines (NICE NG143, AAP 2011) do not favor one drug over the other. Patients pick the one they tolerate better.
- For inflammatory pain (dental, muscular, dysmenorrhea, post-operative), ibuprofen beats paracetamol on NNT in Cochrane reviews.
- For fever in a patient with chronic kidney disease, dehydration, erosive gastritis, or on anticoagulants, paracetamol is the default.
- Combine the two drugs only for severe acute pain or when single-drug therapy fails. Long-term alternation is a bad idea: total liver and kidney load adds up.
- There is no universal "safe dose". Single and daily doses depend on weight, age, and liver/kidney function. Look at the manufacturer's leaflet or the AEMPS prospecto, not at popular articles.
How they work
Paracetamol inhibits COX-2 in the central nervous system and activates serotonergic antinociception. The exact mechanism is still debated, but paracetamol has no peripheral anti-inflammatory effect. That is why it underperforms NSAIDs in arthritis, dysmenorrhea, and post-operative pain (Cochrane Review on paracetamol for acute pain in adults, Toms et al., 2008, updated 2017).
Ibuprofen is a non-selective inhibitor of COX-1 and COX-2 in peripheral tissues. It blocks prostaglandin synthesis at the site of inflammation, which explains both the effect on swelling and pain and the side effects: GI mucosal injury, renal artery constriction, blood pressure elevation, and suppression of the antiplatelet effect of low-dose aspirin.
The whole list of indications, contraindications, and risk groups follows from this mechanistic difference.
Choosing for fever
Fever is a defense response, not a number to drive down at all costs. NICE NG143 (Fever in under 5s, 2019) and the AAP Clinical Report on Fever (2011) agree: antipyretics are for comfort, not for the thermometer reading. An active, well-hydrated child with 38.5 °C does not need treatment by definition.
In head-to-head trials in children over 3 months, the Cochrane review by Perrott et al. (2004) showed slightly faster temperature drop on ibuprofen in the first 2-4 hours. There is no clinically meaningful difference in comfort or illness duration. The Russian Pediatric Society guidelines on URTI list the same two drugs as the basis of antipyretic care.
Antipyretics in infants under 3 months are not used without a doctor's exam. Bacterial infection at this age needs a workup, not symptomatic treatment.
In adults with a common cold, the choice comes down to tolerance. In influenza with myalgia and body aches, ibuprofen subjectively works better because of its anti-inflammatory effect. In an uncomplicated cold, most patients notice no difference.
Choosing for pain
| Pain type | Stronger option | Source |
|---|---|---|
| Tension headache | Ibuprofen 400 mg ≈ paracetamol 1000 mg | Cochrane Derry et al., 2017 |
| Migraine, mild to moderate | Ibuprofen 400 mg > paracetamol 1000 mg | NICE CG150, 2012 |
| Post-extraction dental pain | Ibuprofen 400 mg > paracetamol 1000 mg by NNT | Cochrane Bailey et al., 2013 |
| Primary dysmenorrhea | NSAIDs first line, paracetamol weaker | Cochrane Marjoribanks et al., 2015 |
| Post-operative pain | Ibuprofen + paracetamol > either alone | Cochrane Derry et al., 2013 |
| Osteoarthritis | NSAIDs short courses, paracetamol weaker than expected | NICE NG226, 2022 |
| Musculoskeletal pain | Topical NSAIDs first, systemic NSAIDs if needed | NICE CG177 |
Paracetamol was long considered first-line in osteoarthritis. NICE revised the recommendation in 2022 (NG226): the evidence for long-term paracetamol in large-joint OA is too weak, in contrast to topical and systemic NSAIDs.
For migraine and muscle pain, ibuprofen wins because of the anti-inflammatory component, which paracetamol does not have.
Safety: where "over the counter" ends
GI tract. Ibuprofen raises the risk of erosions, ulcers, and GI bleeding. The relative risk of bleeding in the Castellsague et al. meta-analysis (Drug Saf, 2012) is about 2.7. Paracetamol carries no such risk. In patients with erosive gastritis, peptic ulcer, or GERD, ibuprofen is either avoided or covered with a proton pump inhibitor.
Kidneys. Ibuprofen lowers renal blood flow by suppressing the prostaglandins that keep afferent arterioles dilated. In patients with dehydration, chronic kidney disease, the elderly, and those on a combination of ACE inhibitor or ARB plus diuretic, the "triple whammy" (NICE CKS NSAIDs, 2024) brings a risk of acute kidney injury. Paracetamol has no effect on renal hemodynamics.
Liver. Paracetamol becomes hepatotoxic above 4 g per day, in patients with chronic liver disease, or with chronic alcohol use. WHO recommends staying under 60 mg per kg per day in children. Ibuprofen hepatotoxicity is rare and usually idiosyncratic.
Bleeding and platelets. Ibuprofen inhibits platelet aggregation. On warfarin, rivaroxaban, apixaban, dabigatran, clopidogrel, and low-dose aspirin, ibuprofen is given only in short courses and with medical supervision. Long-term paracetamol above 2 g per day also raises INR in patients on warfarin and needs INR monitoring (BMJ, Hughes et al., 2011).
Pregnancy. Paracetamol is the drug of choice across all trimesters (ACOG, EMA Statement 2019). The FDA in 2020 restricted ibuprofen after 20 weeks because of the oligohydramnios risk, and it is contraindicated in the third trimester due to premature closure of the ductus arteriosus.
Aspirin-exacerbated respiratory disease. Bronchospasm on NSAIDs hits 5-10% of asthma patients, mostly those with nasal polyposis and aspirin intolerance. Ibuprofen is the same trigger as aspirin. Paracetamol is usually safe in this group.
When to hold ibuprofen
- CKD stage C3 and worse (eGFR below 60 mL/min)
- Erosive gastritis or peptic ulcer history
- On anticoagulants or antiplatelets without PPI cover and supervision
- Heart failure (sodium retention, decompensation)
- Hypertension uncontrolled on lisinopril, losartan, or valsartan: ibuprofen blunts their effect
- After 20 weeks of pregnancy
- In the first 6 months after MI or ischemic stroke. Short courses are possible only under physician supervision.
- History of aspirin-exacerbated respiratory disease
When to hold paracetamol
- Chronic liver disease Child-Pugh B or C
- Chronic alcohol use. The FDA Drug Safety Communication (2009) lowers the safe daily dose for patients drinking more than three units per day.
- Glutathione-depleting states: prolonged fasting, severe infection, postoperative fasting
- Long-term use with warfarin above 2 g per day. INR monitoring required.
Combining or alternating
Alternating for fever. AAP 2011 and NICE NG143 do not recommend routine alternation of paracetamol and ibuprofen in children. The Saghir et al. trial (BMJ, 2008) found no meaningful comfort gain over single-drug therapy. In practice, alternation is more often a "way to give parents a sense of control" than a clinical tactic. Dosing mistakes happen more often in tired parents alternating two drugs.
Combining for severe acute pain. The logic flips. The Cochrane review by Derry et al. (2013) for post-operative pain reports an NNT of 1.5 for ibuprofen 400 mg + paracetamol 1000 mg, against an NNT of 2.5 for each drug alone. In other words, 2 out of every 3 patients get meaningful pain relief on the combination versus 1 in 3 on monotherapy. This combination is used after wisdom tooth extraction, for the first 1-2 days after minor surgery, and for severe muscle pain.
Combining the two drugs longer than 3-5 days is a bad idea. Liver load from paracetamol and GI/renal load from ibuprofen add up.
Doses and duration
International sources do not give a universal "safe dose" because single and daily doses depend on weight, age, kidney and liver function, and concurrent medications.
General reference points from FDA Drug Facts and AEMPS prospecto for over-the-counter use in healthy adults:
- Ibuprofen: single 200-400 mg, daily OTC up to 1200 mg. With a prescription and an anti-inflammatory goal, doctors go to 2400-3200 mg per day under supervision.
- Paracetamol: single 500-1000 mg, daily up to 3 g. The EMA cap is 4 g, but the FDA lowered the OTC recommendation to 3 g in 2011 because of hepatotoxicity reports.
Duration of OTC use is up to 3 days for fever and up to 5 days for pain. Beyond that, see a doctor.
Pediatric doses are calculated per kilogram of body weight. Use the leaflet or AEMPS prospecto, not a stranger's anecdote.
What to pick on the shelf
Paracetamol: Tylenol (US), Panadol (UK/EU), Doliprano (FR), Efferalgan (FR/EU), Calpol (UK pediatric). Combination cold-and-flu sachets (Theraflu, Lemsip, Coldrex) usually contain 500-650 mg paracetamol per sachet plus phenylephrine and vitamin C. If a patient also takes paracetamol as an antipyretic on the same day, the dose easily reaches hepatotoxic levels.
Ibuprofen: Advil, Motrin, Nurofen, Brufen. Pediatric ibuprofen suspension: Nurofen for Children, Motrin Infant Drops, Ibuprofeno Cinfa (ES).
Be careful with "stronger" NSAIDs: nimesulide, ketorolac, diclofenac hit harder on pain, but their side-effect profile is also worse. The EMA limits nimesulide to 15 days of treatment because of hepatotoxicity. Ketorolac is not prescribed beyond 5 days. These drugs are not "better ibuprofen": they are tools for narrower indications.
Topical NSAIDs (diclofenac or ibuprofen gel, patch) for musculoskeletal pain work almost as well as systemic, without the GI risk. NICE CG177 recommends them first-line in hand and knee OA.
What not to combine
With ibuprofen:
- Other NSAIDs (nimesulide, ketorolac, diclofenac): double COX blockade, sharp GI risk
- Anticoagulants and antiplatelets (warfarin, rivaroxaban, apixaban, dabigatran, clopidogrel, aspirin): bleeding risk
- ACE inhibitor or ARB (lisinopril, enalapril, ramipril, losartan, valsartan) plus a diuretic (furosemide, indapamide, torasemide): the "triple whammy" on kidneys
- Methotrexate: ibuprofen reduces renal clearance of methotrexate, toxicity rises
- Lithium: same mechanism, blood lithium rises
With paracetamol:
- Regular alcohol: hepatotoxicity
- Warfarin long-term above 2 g per day: INR rises
- Isoniazid, rifampicin, and other CYP inducers: theoretical rise in toxic metabolites, but clinical relevance is limited
Bottom line
The question is not "which one is stronger" but "which one fits this patient with this problem".
Paracetamol is safer for GI and kidneys, riskier for the liver, and does not treat inflammation. Default choice in fever, in pregnancy, in patients with CKD, gastritis, or on anticoagulants.
Ibuprofen wins on anti-inflammatory effect, but it is harder on the GI tract, kidneys, and blood pressure. Default choice in inflammatory and dental pain, in dysmenorrhea, in the first days after minor surgery.
The two drugs combine well only for severe acute pain and only for short courses. Every other "alternation life hack" has no evidence behind it.
Educational reference. This article is not medical advice and does not replace a consultation with a doctor. Treatment decisions belong with the treating physician, especially for patients with chronic conditions or on regular medications. If you are unsure which drug fits your case, ask for a second opinion from a primary care doctor, pediatrician, or clinical pharmacologist.