BACKGROUND/AIMS: The effectiveness of curative therapy for Helicobacter pylori (H. pylori) infection may vary according to the eradication rate, side effects, and compliance of regimen. Lansoprazole, one of proton-pump inhibitor, has been claimed to have greater anti-H. pylori activity than that of omeprazole in vitro. However, there is no literature concerning the comparison of therapeutic efficacy of these two drugs in Korea. Thus, we investigated the efficacy of combination therapy with amoxicillin, metronidazole, and either lansoprazole or omeprazole. METHODS: Eighty Patients with H. pylori infection were treated with one of four regimens: lansoprazole 30 mg UID, amoxicillin 1.0 g BID (LA); lansoprazole 30 mg UID, amoxicillin 1.0 g BID, metronidazole 250 mg TID (LAM); omeprazole 20 mg BID, amoxicillin 1.0 g BID (OA); omeprazole 20 mg BID, amoxicillin 1.0 g BID, metronidazole 250 mg TID (OAM), for 14 days. RESULTS: The eradication rates were 33.3% in LA, 50.0% in OA, 76.5% in LAM and 83.3% in OAM. The most frequently observed side effect was diarrhea or loose stool. CONCLUSIONS: Low dose lansoprazole-based regimen showed comparable eradication rate, side effects and compliance, as compared with omeprazole-based regimen. Further study using lansoprazole at various doses may be needed to evaluate the efficacy of anti-H. pylori eradication regimens in Korea.