DESCRIPTION: This American Gastroenterological Association (AGA) Institute Clinical Practice Update (CPU) aims to review the available evidence and provide expert advice regarding advances in per-oral endoscopic myotomy (POEM). METHODS: This CPU was commissioned and approved by the AGA Institute CPU Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPU Committee and external peer review through standard procedures of Gastroenterology. This review is framed around best practice advice points agreed upon by the authors, based on the current available evidence and expert opinion in this field. Because systematic reviews were not performed, these best practice advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Patients evaluated for POEM should undergo a comprehensive diagnostic workup, which includes clinical history and review of medications, upper endoscopy, timed barium esophagram, and high-resolution manometry. Endoscopic functional luminal impedance planimetry can be a useful adjunct test, particularly in cases when diagnosis is equivocal. BEST PRACTICE ADVICE 2: POEM, laparoscopic Heller myotomy, and pneumatic dilation are effective therapies for type I and type II achalasia; the decision between these treatment modalities should be based on shared decision making, taking into account patient and disease characteristics, patient preferences, and local expertise. POEM should be considered the preferred treatment for type III achalasia. BEST PRACTICE ADVICE 3: Patients with esophagogastric outflow obstruction alone and/or nonachalasia spastic disorders on manometry should undergo a comprehensive evaluation with correlation of symptoms. Evidence for POEM for these manometric findings are limited and should only be considered on a case-by-case basis after other less invasive approaches have been exhausted. BEST PRACTICE ADVICE 4: A single dose of antibiotics at the time of POEM may be sufficient for antibiotic prophylaxis. BEST PRACTICE ADVICE 5: POEM can be performed via either an anterior or posterior tunnel orientation, with comparable efficacy, safety, and rate of postprocedure reflux between these 2 approaches. Endoscopist's preferences and patient's surgical history, including prior laparoscopic Heller myotomy and/or POEM, should be considered when determining tunnel orientation. BEST PRACTICE ADVICE 6: The optimal length of the myotomy in the esophagus and cardia, as it pertains to treatment efficacy and risk for postprocedure reflux, remains to be determined. Adjunct techniques, including real-time intraprocedure functional luminal impedance planimetry, may be considered to tailor or confirm the adequacy of the myotomy. BEST PRACTICE ADVICE 7: The clinical impact of routine esophagram or endoscopy immediately post-POEM remains unclear. Testing can be considered based on local practice preferences, and in cases in which intraprocedural events or postprocedural findings warrant further evaluation. BEST PRACTICE ADVICE 8: Same-day discharge after POEM can be considered in select patients who meet discharge criteria. Patients with advanced age, significant comorbidities, poor social support, and/or access to specialized care should be considered for hospital admission, irrespective of symptoms. BEST PRACTICE ADVICE 9: Pharmacologic acid suppression should be strongly considered in the immediate post-POEM setting, given the increased risk of postprocedure reflux and esophagitis. BEST PRACTICE ADVICE 10: All patients should undergo monitoring for gastroesophageal reflux disease after POEM. Patients with persistent esophagitis and/or reflux-like symptoms despite proton pump inhibitor use, should undergo additional testing to evaluate for other etiologies besides pathologic acid exposure and management to optimize and achieve reflux control. BEST PRACTICE ADVICE 11: Long-term postprocedure surveillance is encouraged to monitor for progression of disease and complications of gastroesophageal reflux disease. BEST PRACTICE ADVICE 12: POEM may be superior to pneumatic dilation for patients with failed initial POEM or laparoscopic Heller myotomy; however, the decision among treatment modalities should be based on shared decision making between the patient and physician, taking into account risk of postprocedural reflux, need for repeat interventions, patient preferences, and local expertise.