To compare the efficacy and safety of aceclofenac (AC) and tenoxicam (TX) in the treatment of rheumatoid arthritis (RA), a multicentric parallel, randomized, double-blind trial of three months duration was performed in 292 patients: 145 were randomized to the AC treatment group and 147 to the TX treatment group. The trial was completed by 237 (81.1%) patients. Both treatment groups showed amelioration of clinical parameters monitored at 15 days, and this improvement continued until the end of the trial, no statistically significant differences being observed between AC and TX. Twenty-four patients (8.2%, 12 AC and 12 TX) did not complete the trial because of inefficacy, and 15 because of side effects (5.1%, 6 AC and 9 TX), in 7 of them due to gastrointestinal intolerance (2,4%, 1 AC, 6 TX, p = 0.052). These data demonstrate that AC shows similar efficacy to TX in the treatment of rheumatoid arthritis and better safety profile than TX, mainly regarding gastrointestinal tolerability.