Objective To assess the efficacy and safety of the endoscopic anti-reflux mucosectomy for gastroesophageal reflux disease. Methods Data of 18 patients with gastroesophageal reflux disease who underwent endoscopic anti-reflux mucosectomy at the First Affiliated Hospital of ZhengZhou University from December 2015 to July 2018 were retrospectively studied. The therapeutic effects (improvement of heartburn and reflux symptoms, 24 h esophageal pH monitoring) and complications were analyzed. Results Anti-reflux mucosectomy was performed successfully in all patients with successful rate of 100%. ESD was performed in 8 cases and EMR in 10 cases.24 h esophageal pH monitoring results showed that the Demeester score, the time percentage of pH < 4, total reflux events and reflux times of pH < 4 with time longer than 5 minutes after treatment were significantly lower than those before treatment (20.16±9.12 VS 74.16±20.03, (2.70±0.88)% VS (6.42±1.37)%, 43.78±19.68 VS 156.56±41.22, 2.89±1.68 VS 9.89±2.95, all P＜0.05). No bleeding, perforation or infection was observed after the procedure. During a follow-up period of 3-34 months, symptom relief rate was 89% (16/18). A tightened cardiac was noted in 18 cases and recovery of mucosal damage was found in 16 patients. Conclusion Anti-reflux mucosectomy is safe, effective and easy to operate for gastroesophageal reflux disease.