Background and study aims Per-oral endoscopic myotomy (POEM) is associated with a short-term clinical response of 82 % to 100 % in treatment of patients with achalasia. Data are limited on the long-term durability of the clinical response in these patients. The aim of this study was to determine the long-term outcomes of patients undergoing POEM for management of achalasia. Methods This was a retrospective multicenter cohort study of consecutive patients who underwent POEM for management of achalasia. Patients had a minimum of 4 years follow-up. Clinical response was defined by an Eckardt score ≤ 3. Results A total of 146 patients were included from 11 academic medical centers. Mean (± SD) age was 49.8 (± 16) years and 79 (54 %) were female. The most common type of achalasia was type II, seen in 70 (47.9 %) patients, followed by type I seen in 41 (28.1 %) patients. Prior treatments included: pneumatic dilation in 29 (19.9 %), botulinum toxin injection in 13 (8.9 %) and Heller myotomy in seven patients (4.8 %). Eight adverse events occurred (6 mucosotomies, 2 pneumothorax) in eight patients (5.5 %). Median follow-up duration was 55 months (IQR 49.9-60.6). Clinical response was observed in 139 (95.2 %) patients at follow-up of ≥ 48 months. Symptomatic reflux after POEM was seen in 45 (32.1 %) patients, while 35.3 % of patients were using daily PPI at 48 months post POEM. Reflux esophagitis was noted in 16.8 % of patients who underwent endoscopy. Conclusion POEM is a durable and safe procedure with an acceptably low adverse event rate and an excellent long-term clinical response.