BACKGROUND/AIMS: Because treatment duration directly influences both patient compliance and side effects in the eradication of Helicobacter pylori (H. pylori), shortening the duration remains the main goal of therapeutic strategies. The aim of the present study was to evaluate the efficacy and safety of short-term regimen (weekend therapy) for curing the H. pylori infection. METHODS: Twenty-eight patients with H. pylori-positive peptic ulcer received omeprazole 40 mg once daily for 7 days (from Monday to Sunday), bismuth 240 mg q.i.d., amoxicillin 1 g q.i.d., and metronidazole 500 mg q.i.d. for only 2 days (Saturday and Sunday). We compared the eradication rate with that of seventy-eight patients with H. pylori-positive peptic ulcer who had received either OAC (omeprazole, amoxicillin, and clarithromycin) or BMA (bismuth, metronidazole, and amoxicillin) regimens during the same period. H. pylori infection was assessed before treatment by rapid urease test or histologic examination. Four weeks after the end of treatment, the infection was also assessed by rapid urease test, histologic examination or urea breath test in weekend group and by urea breath test in control group. RESULTS: H. pylori eradication rates were 61.1% by per-protocol analysis and 39.3% by intention-to-treatment analysis. There were no treatment associated serious side effects, and only one patient (5.6%) showed mild epigastric discomfort. All patients completed the course of treatment. CONCLUSIONS: Weekend therapy have relatively low eradication rate, however, this therapeutic approach is safe and shows good compliance for the treatment of H. pylori infection.