BACKGROUND/AIMS: It is not clear whether the anti-secretory therapy should be continued for symptomatic relief and ulcer healing before or after the eradication of H. pylori in patients with peptic ulcer disease. The aim of this study was to evaluate the effectiveness of additional anti-secretory therapy before or after H. pylori eradication in peptic ulcer disease. METHODS: Thirty eight patients with H. pylori-positive active peptic ulcer were included. Patients were randomly allocated into 3 groups; standard 1-week triple therapy followed by omeprazole (20 mg, qd) for 3 weeks (group A), standard 1-week triple therapy only (group B), and omeprazole (20 mg, qd) for 3 weeks followed by 1-week triple therapy (group C). Endoscopy with the rapid urease test and histology for H. pylori was performed 4-8 weeks after the completion of treatment. The symptom was scored by a visual analog scale. RESULTS: Of the 38 patients, 10 were excluded from the per-protocol analysis of this study. The H. pylori eradication rates were 87.5% (group A), 80.0% (group B) and 90.0% (group C) respectively. The peptic ulcer healing rates were 100% in group A, 70.0% in group B, and 90.0% in group C. There was no difference in H. pylori eradication rates and ulcer healing rates among three groups (p>0.05). Symptom score differences between pre-treatment and post-treatment group were not significantly different (p>0.05). CONCLUSIONS: The standard one week triple therapy with or without 3-weeks anti-secretory treatment with omeprazole before or after the therapy does not affect H. pylori eradication rates, peptic ulcer healing rates, and symptom score improvement.