This multicenter double-blind clinical trial compared the efficacy and safety of benoxaprofen and naproxen in the treatment of rheumatoid arthritis. The studies followed a crossover design which provided 6 wk therapy with each of the 2 study drugs. Benoxaprofen at a single daily dose of 600 mg compared favorably to naproxen, 750 mg, administered in 2 equally divided doses. All efficacy results indicated slightly more improvement with benoxaprofen although the difference between the 2 drugs was not significant. Side effects were generally mild and only 1 patient discontinued benoxaprofen therapy because of a reactivation of a duodenal ulcer.