GOAL: To determine the risk factors associated with post-per-oral endoscopic myotomy (POEM) Gastroesophageal Reflux Disease (GERD). BACKGROUND: Per-oral endoscopic myotomy (POEM) has become a standard treatment for achalasia, but post-procedure GERD remains a significant clinical concern. Current studies lack consistency in defining risk factors for GERD postprocedurally. STUDY: We conducted a retrospective review of patients who underwent POEM at a tertiary-care center over a 10-year period. Demographic, clinical, manometric, endoscopic, and procedural data were collected. A binary logistic regression was performed to identify independent predictors of GERD symptoms or acid-reducing medicine post-POEM. RESULTS: Of 296 patients (53.4% male; mean age: 57±18 y; mean BMI: 27.4±6.4), most had type II achalasia (54%). Procedures were primarily performed by one gastroenterologist (93.2%) using an anterolateral approach (93.2%). Eckardt scores significantly improved post-procedure. Independent predictors of post-POEM GERD symptoms or medication use included older age (OR: 1.02; 95% CI: 1.00-1.04; P=0.03), smoking history (OR: 2.66; 95% CI: 1.17-6.05; P=0.01), post-POEM BMI increase (OR: 2.49; 95% CI: 1.05-5.94; P=0.03), full-thickness myotomy (OR: 6.85; 95% CI: 2.09-22.37; P=0.001), and nonachalasia indication (OR: 9.88; 95% CI: 1.09-88.96; P=0.04). De novo GERD was observed in 29 patients (9.7%), with smoking (OR: 41.38, 95% CI: 2.54-673.71, P<0.01) and full-thickness myotomy (24.1% vs. 5.9%, P<0.01) as independent risk factors. CONCLUSIONS: Post-POEM GERD represents a heterogeneous group. Older age, smoking history, nonachalasia diagnosis, full-thickness myotomy, and postprocedure weight gain increase GERD risk. The results of this study require further validation through multicenter collaboration.