The efficacy and tolerability of aceclofenac (100 mg bid; n = 109), a new non-steroidal anti-inflammatory agent, was compared to that of indomethacin (50 mg bid; n = 110) in a multi-centre, 12-week, randomized, double-blind clinical trial in patients with rheumatoid arthritis. The efficacy of aceclofenac, on the basis of several clinical features characteristic for rheumatoid arthritis, was comparable to that of indomethacin. Patients in both treatment groups showed a notable and significant improvement during the study. Under aceclofenac treatment, the number of painful and swollen joints decreased by a median of six and nine, respectively, morning stiffness was shortened by 1 h, and the grip strength of both hands increased by a median of 8 mmHg. Pain at rest was relieved in 65.3% of aceclofenac-treated patients and in 67.1% of those treated with indomethacin (n.s.). With regard to safety, aceclofenac tended to be better tolerated than indomethacin. Among the 109 aceclofenac-treated patients, 26 incidents of adverse effects due to the drug were noted in 20 patients (18.4%). Sixty-four incidents of adverse events were documented in 32 (29.1%) of the 110 patients treated with indomethacin. The most common adverse events reported during treatment with aceclofenac were heartburn (four patients) and vertigo (three patients).