In a double blind, randomized, parallel group study, 197 patients with osteoarthritis (OA) received nabumetone (1000 mg/day) or indomethacin (75 mg/day) for 6 weeks and doses could be doubled. Doubling the dose resulted in a 100 or 67% increase in pain relief with nabumetone or indomethacin, respectively. Significantly more patients experienced at least 1 severe adverse event with indomethacin than with nabumetone. With nabumetone, the incidence of adverse events did not increase with dose. However, with the increase in dose, the incidence of all adverse events and gastrointestinal events increased in indomethacin treated patients. Nabumetone was as effective as indomethacin for the treatment of OA. However, significantly fewer nabumetone treated patients experienced severe adverse events and the frequency of events did not increase with dose.