BACKGROUND: A prospective, randomized trial proved that Helicobacter pylori eradication significantly reduces the incidence of metachronous gastric cancer during a 3-year follow-up. OBJECTIVE: To investigate the long-term effect of H pylori eradication on the incidence of metachronous gastric cancer after endoscopic resection of early gastric cancer. DESIGN: Retrospective, multicenter study. SETTING: Kyushu University Hospital and 6 other hospitals in Fukuoka Prefecture, Japan. PATIENTS AND INTERVENTIONS: Follow-up data for 268 H pylori-positive patients who had undergone endoscopic resection of early gastric cancer were retrospectively investigated. A total of 177 patients underwent successful H pylori eradication (eradicated group), whereas 91 had persistent H pylori infection (persistent group). MAIN OUTCOME MEASUREMENTS: The incidence of metachronous gastric cancer was compared in these 2 groups. RESULTS: When the follow-up period was censored at 5 years, the incidence rate in the eradicated group was lower than that observed in the persistent group (P = .007). During the overall follow-up period ranging from 1.1 to 11.1 years (median 3.0 years), metachronous gastric cancer developed in 13 patients (14.3%) in the persistent group and in 15 patients (8.5%) in the eradicated group (P = .262, log-rank test). Based on a multivariate logistic regression analysis, baseline severe mucosal atrophy and a follow-up of more than 5 years were found to be independent risk factors for the development of metachronous gastric cancer. LIMITATIONS: Retrospective study. CONCLUSIONS: H pylori eradication does not reduce the incidence of metachronous gastric cancer. H pylori eradication should be performed before the progression of gastric mucosal atrophy.