Roxatidine is a structurally novel histamine 2-receptor antagonist. This randomized, double-blind trial compared duodenal ulcer healing rates after 4 and 8 weeks of treatment with a twice-daily regimen of either 75-mg roxatidine (n = 69) or 150-mg ranitidine (n = 70). Endoscopy was performed at 4- and 8-week intervals to assess ulcer healing. Symptom severity scores and side effects were recorded. In the intent-to-treat analysis after 4 weeks, 77.3% of patients were healed with roxatidine and 75.8% were healed with ranitidine; after 8 weeks, the healing rates were 93.9% and 81.8%, respectively. There were no significant differences between groups. In the per-protocol analysis at 4 weeks, 80.3% of patients were healed with roxatidine and 83.1% were healed with ranitidine; after 8 weeks, the healing rates were 95.1% and 88.1%, respectively. There were no significant differences between groups. Both agents effectively suppressed ulcer symptoms. The average number of antacid tablets consumed daily to relieve ulcer pain and compliance rates for trial drugs were similar between groups. Adverse events primarily included a few occurrences of exacerbated pain. We conclude that roxatidine is at least as good as ranitidine for short-term management of duodenal ulcer in terms of ulcer healing and symptom resolution. It also causes few adverse effects.