Objectives To compare the effi cacy and safety of single versus combination non-prescription oral analgesics in community-derived people aged 40 years and older with chronic knee pain. Methods A randomised, double-blind, four-arm, parallelgroup, active controlled trial investigating short-term (day 10) and long-term (week 13) benefi ts and sideeffects of four regimens, each taken three times a day: ibuprofen (400 mg); paracetamol (1000 mg); one fi xeddose combination tablet (ibuprofen 200

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... acetamol 500 mg); two fi xed-dose combination tablets (ibuprofen 400 mg/paracetamol 1000 mg). Results There were 892 participants (mean age 60.6, range 40-84 years); 63% had radiographic knee osteoarthritis and 85% fulfi lled American College of Rheumatology criteria for osteoarthritis. At day 10, two combination tablets were superior to paracetamol (p<0.01) for pain relief (determined by mean change from baseline in WOMAC pain; n=786). At 13 weeks, signifi cantly more participants taking one or two combination tablets rated their treatment as excellent/ good compared with paracetamol (p=0.015, p=0.0002, respectively; n=615). The frequency of adverse events was comparable between groups. However, by 13 weeks, decreases in haemoglobin (≥1 g/dl) were observed in some participants in all groups. Twice as many participants taking two combination tablets had this decrease compared with those on monotherapy (p<0.001; paracetamol, 20.3%; ibuprofen, 19.6%; one or two combination tablets, 24.1%, 38.4%, respectively). Conclusions Ibuprofen/paracetamol combination analgesia, at non-prescription doses, confers modest short-term benefi ts for knee pain/osteoarthritis. However, in this population, paracetamol 3 g/day may cause similar degrees of blood loss as ibuprofen 1200 mg/day, and the combination of the two appears to be additive.