ObjectivesMinimally invasive treatments have been applied for gastroesophageal reflux disease (GERD), but the long‐term results are controversial. Antireflux mucosectomy (ARMS) is a simple endoscopic procedure that does not require the insertion of a foreign body. We provide the first report on the long‐term results of ARMS.MethodsThis was a single‐center, single‐arm trial, prospective study of 88 patients with proton pump inhibitor (PPI)‐refractory GERD who underwent ARMS between June 2012 and June 2017. Primary outcomes were the rates of long‐term effectiveness and PPI discontinuation. Secondary outcomes were to compare patients' preoperative background characteristics, questionnaire, and multichannel intraluminal impedance and pH monitoring data to examine the predictive factors of ARMS. The clinical course was reviewed, including the need for additional treatment after ARMS.ResultsAntireflux mucosectomy produced a long‐term effect in 68.3% of the patients, and PPI could be discontinued in 42% of patients. There were significant differences in age, intensity of preoperative symptoms, and acid‐related indicators. Forty‐five percent (27/60) had reflux hypersensitivity and ARMS provided long‐term effectiveness in 81% of these patients. There was no significant difference in subjective symptom assessment between those with short‐term and long‐term efficacy. Additional treatment was administered in 23% (14/60) and scheduled at 1–2 years’ follow‐up.ConclusionsAntireflux mucosectomy showed long‐term efficacy, and many of the cases with short‐term effects were able to maintain them. In addition, ARMS is also effective in patients with reflux hypersensitivity, and provides a treatment option that bridges the gap between surgical and medical treatment.