Abstract 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.