BACKGROUND/AIMS: Some patients are refractory to the usual triple therapy for eradication of Helicobacter pylori, consisting of a proton pump inhibitor, amoxicillin and clarithromycin, so there needs to be an alternative strategy for retreatment after failure to eradicate the infection. METHODOLOGY: The study group comprised 17 H. pylori-positive patients who had failed to clear H. pylori infection after 1 week of treatment with usual doses of proton pump inhibitor, amoxicillin and clarithromycin. The sensitivity of H. pylori to clarithromycin and amoxicillin, and the CYP2C19 genotype status of each patient were determined and treatment with rabeprazole (10 mg qid) and amoxicillin (500 mg qid) for 2 weeks was started. RESULTS: Eleven patients were infected with a clarithromycin-resistant strain of H. pylori. Twelve patients had the homozygous extensive metabolizer genotype, 5 had the heterozygous extensive metabolizer genotype and there were none with the poor metabolizer genotype of CYP2C19. All patients were successfully cleared of their H. pylori infection without any adverse effects, irrespective of CYP2C19 genotype status (100%, 95% confidence interval: 76-100%). CONCLUSIONS: High-dose dual therapy with rabeprazole (10 mg qid) and amoxicillin (500 mg qid) for 2 weeks appears useful treatment strategy after failure of eradication of H. pylori by the usual triple proton pump inhibitor/amoxicillin/clarithromycin therapy.