OBJECTIVES: Some patients with gastroesophageal reflux disease (GERD) are refractory to proton pump inhibitor (PPI) therapy. Anti-reflux mucosectomy (ARMS) is a minimally invasive endoscopic procedure for treatment of GERD. In this study, we retrospectively evaluated the outcomes of ARMS performed in patients with PPI-refractory GERD at our institution. METHODS: A total of 109 patients with PPI-refractory GERD who underwent ARMS were retrospectively reviewed. Pre- and post-ARMS questionnaire scores, acid exposure time (AET), DeMeester score, proximal extent, and PPI discontinuation rate were compared. RESULTS: There was a significant improvement in the symptom score (P < 0.01) and 40-50% of patients were able to discontinue PPI after ARMS. In patients who were followed up for 3 years, sustained improvement in subjective symptoms was observed. AET and DeMeester score significantly improved after ARMS (P < 0.01); however, there was no significant improvement in proximal extent (P = 0.0846). CONCLUSIONS: Anti-reflux mucosectomy is an effective minimally invasive therapy for patients with PPI-refractory GERD. The therapeutic efficacy is attributable to suppression of acid backflow due to contraction of the scar tissue in cardia.