Low-dose ibuprofen is as effective as aspirin and paracetamol for the indications normally treated with over-the-counter (OTC) medications and is associated with the lowest risk of gastrointestinal toxicity of any non-steroidal anti-inflammatory drug. By contrast, even low-dose aspirin is associated with an appreciable risk of gastrointestinal toxicity. Paracetamol is well tolerated and effective in treating mild to moderate pain but there is growing concern about a possible risk of gastrointestinal toxicity and a possible link with asthma in children. The PAIN (Paracetamol, Aspirin, Ibuprofen New tolerability) study was a blinded randomised comparison of the tolerability of OTC analgesics in the treatment of common types of acute pain encountered in the community. A total of 8,677 adults were randomised to treatment with ibuprofen 1200 mg/day, paracetamol 3 g/day or aspirin 3 g/day for 1-7 days. The most common indications for treatment were musculoskeletal conditions (31-33%), colds or flu (19-20%), backache (15-17%), sore throat (11-12%) and headache (10-11%). Significant adverse events were more common with aspirin (10.1%) than ibuprofen (7.0%) (P<0.001) or paracetamol (7.8%). Significant gastrointestinal events were less frequent with ibuprofen (4.0%) than with aspirin (7.1%, P<0.001) or paracetamol (5.3%) (P=0.025). For every 100 patients treated, five more will experience significant adverse events if they are taking aspirin rather than ibuprofen, and four more than if they were taking paracetamol.