To study nabumetone (1,000 mg once daily) by comparison with piroxicam (20 mg once daily) in patients with osteoarthritis, a randomized, double-blind trial was set up in 40 general practices. Evaluation was based on clinical outcome in 198 patients. There was some evidence that nabumetone is associated with a lower and less severe occurrence of gastric pain, and with more withdrawals due to lack of efficacy. Although the differences between nabumetone and piroxicam were small in this study, these were clinically relevant. The general practitioner should balance the respective benefits of greater safety and tolerance against greater efficacy in meeting the requirements of an individual patient with osteoarthritis.