The relationship between Helicobacter pylori (H. pylori) infection and gastro-esophageal reflux disease (GERD) is complex. Since some studies have suggested that H. pylori eradication may result in an increased incidence of GERD in duodenal ulcer patients, there have been debates about the protective function of H. pylori infection on GERD. H. pylori-associated antral gastritis can induce increased gastric acid output via increasing gastrin secretion. Changes in gastric acid secretion depend on the distribution (e.g. antral, corpus or pangastritis) or severity of gastritis, not on H. pylori infection itself. Patients with H. pylori infection are at risk of developing gastric mucosal atrophy, and a cohort study suggested that long-term proton pump inhibitor therapy for GERD may accelerate this process. Therefore, it has been recommended that H. pylori should be treated in GERD patients in whom a long-term antisecretory therapy is planned. The previous hypothesis that 'H. pylori infection protects from the development of GERD' is thought to be an erroneous concept recently.