GOALS: We compared the eradication results of retreatment of eradication with proton pump inhibitor (PPI) plus amoxicillin and metronidazole for patients with Helicobacter pylori infection not eradicated by initial treatment with PPI plus amoxicillin and clarithromycin. BACKGROUND: In Japan, the guideline proposes that the use of metronidazole in a triple therapy containing PPI, PPI plus amoxicillin and metronidazole is desirable in retreatment. However, there are no reports comparing various retreatment using different PPIs. METHODS: After initial treatment failure with a PPI plus amoxicillin and clarithromycin, 169 patients were randomized to a PPI (rabeprazole, lansoprazole, or omeprazole) plus amoxicillin and metronidazole given b.i.d. for 7 days. RESULTS: Pretreatment susceptibility testing showed a high level of clarithromycin resistance (78%). The over all eradication rates were similar with the 3 PPIs, 91.1% range 90.1 to 91.4 with intention-to-treat analysis. The presence of metronidazole resistance reduced the eradication rate by approximately 40% (from 96.6% to 57.1%, P<0.05). CONCLUSIONS: In Japan, the combination of a PPI plus amoxicillin and metronidazole provide excellent eradication rates after initial treatment failure with a PPI plus amoxicillin and clarithromycin. The results with metronidazole resistant strains are less satisfactory and pretreatment susceptibility testing may become needed if the prevalence of metronidazole resistant H. pylori increase.