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Background and study aims Both Heller myotomy (HM) and per-oral endoscopic myotomy (POEM) are efficacious therapies for achalasia. The efficacy and safety of POEM vs HM in Latin America and specifically in patients with Chagas disease is unknown. Patients and methods Consecutive patients undergoing either HM or POEM for achalasia were included from nine Latin American centers in a prospective registry over 5 years. Technical success was defined as undergoing a successful myotomy. Clinical success was defined as achieving an Eckardt score < 3. Data on demographics, procedure info, Eckardt score, and adverse events (AEs) were collected. Student’s t test, Chi squared, and logistic regression analyses were conducted. Results One hundred thirty-three patients were included (59 male; 44 %; mean age 47). POEM was performed in 69 patients, HM in 64 patients. A total of 35 patients had Chagas disease, 17 of 69 in the POEM group, 18 of 64 in the HM group. Both groups had significant reduction in Eckardt scores (P < 0.00001), but successful initial therapy was significantly higher in the POEM group compared to the HM group (P = 0.01304). AEs were similar in both group (17 % vs 14 %) and consisted of pneumothorax (n = 3 vs 2), bleeding requiring transfusion (n = 3 vs 2), and mediastinitis (n = 3 vs 1). Hospital stay was longer in the HM group than in the POEM group (P < 0.00001). In the Chagas subgroup, post-procedure Eckardt score in the POEM group was significantly reduced by 5.71 points (P < 0.00001) versus 1.56 points in the HM group (P = 0.042793). Conclusion Both HM and POEM are efficacious for achalasia, but POEM was associated with higher initial therapy success and shorter hospital stay in Latin America. In Chagas patients with achalasia, POEM was significantly more effective than HM.