In this randomized, double-blind, multicenter study, H. pylori-positive patients with an active duodenal ulcer (DU) received esomeprazole, 20 mg twice daily (bid), or omeprazole, 20 mg bid, with amoxicillin, 1000 mg bid, and clarithromycin, 500 mg bid, for 1 week (EAC and OAC, respectively). Patients received an additional 3 weeks of either placebo or omeprazole, 20 mg once daily (od), in the EAC and OAC groups, respectively. The intent-to-treat population included 374 patients (EAC, 186; OAC, 188). Four-week DU healing rates were similar in the EAC+placebo and OAC+omeprazole groups: 74% and 76%, respectively. DU healing rates at 8 weeks were 87% for EAC+placebo and 88% for OAC+omeprazole. H. pylori eradication rates were 75% and 79% for EAC and OAC, respectively. Both regimens were well tolerated. A 1-week regimen of esomeprazole-based H. pylori eradication triple therapy was as effective for DU healing and eradication of H. pylori as omeprazole-based triple therapy followed by an additional 3 weeks of monotherapy.