Abstract Per oral endoscopic myotomy (POEM) has emerged as a favorable alterative to Heller myotomy for achalasia. However data is limited on the effectiveness in palliation of symptoms in patients who have an esophagus with a sigmoid/tortuous configuration, or a mega-esophagus with width more than 5 cm, due to long-standing achalasia. Our objective is to investigate the outcomes after POEM procedure in patients diagnosed with achalasia and considered end-stage. Methods A retrospective cohort study was conducted in a large hospital between April 2014 and July 2019. A total of 504 patients were identified with 218 undergoing POEM during the study time period of which 57 patients had a sigmoid or tortuous esophagus, and/or had a barium column width of more than 5 cm on timed barium esophagograms (TBE). Primary outcome was symptom relief during follow-up, defined as a post-operative Eckardt score ≤ 3. We also explored integrated resting pressure (IRP) on manometry, barium column height and width on TBE, complications and procedure related parameters. Statistical analyses were performed using R. Results Significant decrease in median Eckardt scores were observed, 7.5 [6,8.8] pre-operatively to 0 [0,1] at 2 months (p < 0.001). At 2 years, 12 of 14 patients (85%), reported scores of ≤3. Improvements at 2 months were noted in median IRP (25.4 mmHg [15.5, 35.9] vs. 4.0 mmHg [2.2,9.0]), 1 min TBE height (11.5 cm [7.5,15.0] vs. 6.8 cm [4.7,9.0]) and width (5.0 cm [4.1,6.1] vs. 2.8 cm [1.9,3.1]), p < 0.001. At 2 years, they were 9.5 cm [5,12.8] and 3.0 cm [2.4,4.5], respectively. Post-operative pH studies in 35(61%) patients demonstrated a DeMeester score ≥ 14.72 in 17(49%) patients. Almost all patients reported return to activities of daily living within 7 days. Conclusion POEM is an effective and safe modality in achalasia patients with end-stage esophagus. Patients in this cohort historically have had poor outcome to interventions and our data shows excellent short-to-medium term outcome with low morbidity after POEM. Given its efficacy, minimal invasiveness and short return to function, POEM is a reasonable first and gold standard palliative therapy in this difficult cohort and should be attempted before considering esophagectomy.