Abstract Background The association between Helicobacter pylori and reflux esophagitis (RE) remains controversial. This study aimed to prospectively evaluate the effect of H. pylori eradication on RE and gastroesophageal reflux (GERD) symptoms in H. pylori-positive patients who underwent endoscopic resection of gastric neoplasm. Methods Of the 244 patients enrolled in this study, 173 H. pylori-positive patients underwent follow-up at least once. We evaluated the prevalence of RE and GERD symptoms in these patients following H. pylori eradication. Results There were 75.7% (131/173), 78.6% (125/159), and 78.9% (105/133) subjects who were successfully eradicated after 6, 12, and 18–24 months, respectively. During the 2-year follow-up period, the eradication of H. pylori did not increase the incidence of RE (OR 0.93; 95% CI, 0.49–1.77, p = 0.828). H. pylori status was also not associated with the development of GERD symptoms (OR 1.12; 95% CI, 0.47–2.95, p = 0.721). In the univariate analysis for RE, present smoking history (OR 4.79; 95% CI 1.98–11.60, p = 0.001), present alcohol consumption history (OR 2.18; 95% CI 1.03–4.63, p = 0.041), and diabetes mellitus (OR 2.44; 95% CI 1.02–5.86, p = 0.045) were found to be associated with RE. Multivariate analysis showed that present smoking history (OR 4.54; 95% CI 1.84–11.02, p = 0.001) was a significant risk factor for RE. Conclusions H. pylori eradication did not increase the incidence of RE or GERD symptoms in patients who underwent endoscopic resection of gastric neoplasm.