The efficacy and safety of aceclofenac (100 mg bid), a new nonsteroidal anti-inflammatory/anti-rheumatic agent, were compared with those of naproxen (500 mg bid) in a multi-centre, twelve-week, randomized, double-blind, parallel-group clinical trial in outpatients with active osteoarthritis of the knee. 190 patients received aceclofenac, 184 naproxen. The two treatments were compared on the basis of several characteristic clinical features of osteoarthritis of the knee, including various pain measurements. In both groups, the treatment resulted in a significant reduction of the pain at rest, pain on movement and the pain from pressure on the joint, 76-86% of aceclofenac patients reporting reduction in pain after 12 weeks. Three-quarters of the aceclofenac-treated patients had an accompanying reduction in joint swelling and 81.4% in knee function capacity, up to complete freedom of movement. Joint stiffness, which at baseline lasted 20 minutes, was reduced in the aceclofenac group to 10 minutes. A statistically significant difference in the efficacy of the two drugs was not found. The 34 adverse drug effects documented in 24 (12.6%) of the aceclofenac patients were fewer than the 43 events in 30 patients (16.3%) reported for naproxen. The trend towards better tolerability of aceclofenac manifested itself above all in a lower total incidence of gastrointestinal side-effects. Aceclofenac is as effective as naproxen in the symptomatic treatment of osteoarthritis of the knee and is well tolerated in general.