We investigated the effects of omeprazole or lansoprazole on peptic ulcer healing, eradication of Helicobacter pylori (Hp) and abdominal symptoms. A prospective, randomized study was performed for the administration of omeprazole or lansoprazole. Hp-positive peptic ulcer patients (n = 86) were randomly assigned to two groups. Gastric ulcer patients received omeprazole 20 mg once daily or lansoprazole 30 mg once daily for 8 weeks. Duodenal ulcer patients were given omeprazole 20 mg once daily or lansoprazole 30 mg once daily for 6 weeks. Endoscopy was performed at baseline, at the end of therapy, and 4 weeks after stopping therapy. The colony factor units (CFUs) of Hp in biopsy specimens were examined. The CFUs of Hp in gastric and duodenal ulcer were significantly decreased at 4 weeks after stopping lansoprazole therapy. We conclude that Hp eradication by combined use of lansoprazole with antibiotics appears to be a promising therapy.