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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 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 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.