One hundred sixty-two patients chronically ingesting ibuprofen, piroxicam, or naproxen for osteoarthritis, who had abdominal pain and an endoscopically proven gastric ulcer were evaluated for eight weeks in a randomized, double-blind trial comparing misoprostol (200 micrograms four times daily with meals and at bedtime) (N = 77) with placebo (N = 85). Patients discontinued their usual daily dose of antiarthritic medication throughout the study period, and an endoscopy was performed at four weeks and eight weeks (if necessary) to assess ulcer healing. Gastric ulcers were defined as circumscribed breaks in the gastric mucosa of 0.3 cm in diameter or greater. Misoprostol therapy significantly accelerated the rate of gastric ulcer healing compared to placebo (P = 0.033). The cumulative percent healed after four and eight weeks of therapy for misoprostol versus placebo were: 83% vs 61% at four weeks and 96% vs 90% at eight weeks (P = 0.0028 and P = 0.0977, respectively by lifetable analysis). Relief of abdominal pain did not differ significantly between the treatment groups. Misoprostol significantly accelerates the healing of ibuprofen-, piroxicam-, or naproxen-induced gastric ulcers.