Background/Aims: Proton pump inhibitor-based triple therapy is the most commonly used H. pylori eradication regimen. Esomeprazole, a new proton pump inhibitor that is the S-isomer of omeprazole, has been shown to be metabolized at a lower rate, resulting in higher plasma levels. We compare the efficacy of esomeprazole and omeprazole for the eradication for H. pylori in patients with duodenal ulcer. Methods: One hundred and forty eight duodenal ulcer patients with H. pylori infection were treated with esomeprazole 20 mg twice daily or omeprazole 20 mg twice daily, in combination with amoxicillin 1,000 mg and clarithromycin 500 mg twice daily for 7 days. The successful H. pylori eradication was confirmed by a negative ¹³C-urea breath test from 4 weeks to 6 weeks after completing therapy. Results: H. pylori eradication rates were comparable for esomeprazole vs. omeprazole(ITT: 90.5% vs. 83.8%; PP: 91.8% vs. 86.1%). The differences in eradication rates were not statistically significant between both groups. No withdrawal due to side-effects were identical in the two groups. Conclusions: Esomeprazole-based triple therapy for 7 days is effective therapy of H. pylori eradication in the patients with duodenal ulcer, and is well tolerated. (Korean J Helicobacter Res Prac 2002;2:188-191)