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Per-oral endoscopic myotomy (POEM) has become the preferred alternative treatment to standard Heller myotomy for patients with esophageal achalasia, in Latin American countries. The aim of our study was to evaluate the efficacy and safety of a POEM in the management of achalasia with and without Chagas disease in patients receiving POEM.Patients who underwent POEM from tertiary centers in Latin America were included in a dedicated registry. Countries included Brazil, Colombia, Ecuador, Mexico, Nicaragua, and Venezuela. Patients enrolled needed to have a preoperative manometry and swallow contrast study confirming achalasia. Clinical success was defined as significant improvement in Eckardt score after therapy.POEM was technically successful in 81/89 (91%) patients (mean age, 44 y). There was a significant decrease in preprocedure and postprocedure Eckardt score from 8.7 (range, 3 to 12) to 2.15 (0 to 10) (P<0.001), preprocedure and postprocedure barium swallow evaluation (98% vs. 89%; P=0.017), and preprocedure and postprocedure lower esophageal sphincter pressure measurement (from 35 to 13.8 mm Hg; P<0.001). Clinical success was achieved in 93% of patients. Patients with Chagas disease (n=58) were 9.5 times more likely to respond to POEM (P=0.0020; odds ratio, 9.5).POEM is an efficacious and safe therapeutic modality for treatment of achalasia in Latin America. Chagas disease-related achalasia seems to particularly respond better to POEM when it is performed by experienced endoscopists.