This six-month, double-blind, controlled, randomized, parallel study at 13 medical centers compared the safety and efficacy of nabumetone (1,000 mg taken at bedtime) with that of naproxen (250 mg twice daily) in the treatment of osteoarthritis in symptomatic adult outpatients. Five efficacy parameters were measured: patients' assessment of overall osteoarthritis activity and pain, physicians' assessment of overall osteoarthritis activity and pain, and physicians' assessment of pain with respect to a declined activity. All 489 patients who took medication were included in the evaluation of safety, and 455 patients (227 in the nabumetone group and 228 in the naproxen group) were evaluated for efficacy. Significant improvement in all five efficacy parameters occurred in both groups. No significant differences were found between the two groups at the end of the study in any of the five efficacy parameters. Twenty-three percent of nabumetone and 17 percent of naproxen patients withdrew from the study for lack of efficacy. At least one possible or probable treatment-related adverse experience was reported for 45 percent of nabumetone-treated patients and 42 percent of those given naproxen, and in 19 percent of the nabumetone-treated and 18 percent of the naproxen-treated patients these experiences were moderate or severe. However, only 7 percent of patients in each group withdrew from the study due to adverse experiences. Nabumetone and naproxen have comparable safety and efficacy, suggesting that a single, nighttime dose of nabumetone is a convenient, effective, and safe treatment for osteoarthritis.