BACKGROUND: Although effective therapies are available for curing Helicobacter pylori infection, the problem persists about what to do for patients who fail two or more treatment courses despite a good compliance. AIM: To test a twice a day midday quadruple therapy as salvage therapy. METHODS: Dyspeptic H. pylori-infected patients who failed two or more courses of anti-H. pylori therapy received omeprazole 20 mg, tetracycline 500 mg, metronidazole 500 mg, and bismuth subcitrate caplets 240 mg twice a day (with the midday and evening meals) for 14 days. H. pylori status was evaluated by 13C-urea breath test and histology 4-6 weeks after therapy. Eradication was defined as no positive test. RESULTS: Seventy-one patients were enrolled and 68 completed the full 14 days of therapy (mean age 46 years; 28 men). Thirty-three patients had failed prior treatment twice, 19 had failed three times, and 16 had failed four or more times. The cure rates were: intention to treat=93% (66/71); (95% CI=84% to 98%), per protocol=97% (66/68); (95% CI=89%- 100%). Success was excellent irrespective of diagnosis, age, prior treatment protocols, or smoking status. Moderate side-effects were experienced by only two patients. CONCLUSION: Midday bismuth subcitrate based twice a day quadruple therapy was an excellent salvage therapy. BID midday quadruple regimen should be considered as the therapy of choice.