In 2003, Inoue et al. observed that a patient undergoing endoscopic mucosal resection across the gastroesophageal junction for Barrett’s esophagus experienced resolution of gastroesophageal reflux disease (GERD) symptoms. This technique was refined and applied to patients with medically refractory GERD and found to improve symptoms and DeMeester scores. The anti-reflux mucosectomy (ARMS) procedure is now seen as an endoscopic alternative to treat patients with medically refractory GERD in the absence of hiatal hernia. Those who qualify for this procedure are able to undergo an outpatient, well-tolerated intervention with documented 70% clinical response rate paired with a relatively low complication rate. Furthermore, ARMS is also able to be employed as a tool for patients who have undergone fundoplication and transoral incisionless fundoplication or have refractory GERD after sleeve gastrectomy and elect against conversion to roux-en-y gastric bypass.