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AIM: To test a strategy for endoscopic submucosal dissection (ESD) training in animal models designed to overcome the initial learning curve. METHODS: ESD was attempted in ex vivo and in vivo pig models. Thirty ESD procedures were attempted in the esophagus ( n = 9) or the stomach ( n = 21). The ex vivo model was used until initial competence was achieved. In the in vivo model, several ESD procedures were performed in up to 3 sessions. The following variables were analyzed: specimen size, complete and en bloc resection rate, time for circumferential incision, time for submucosal dissection, total ESD duration, and complications. RESULTS: Complete resection was achieved in 28 cases ( en bloc 27); 2 could not be completed (one perforation, one technical difficulty). The mean ± SD time for circumferential incision was 36.2 ± 16.8 min (range: 8-87 min), and the mean ± SD time for submucosal dissection was 45.1 ± 35.7 min (range: 9-196 min). The mean ± SD size of the resected specimens was 45.2 ± 17.8 mm. The mean ± SD total resection time was significantly increased for the gastric cases performed in the first half of the study ( n = 13) than in the second half ( n = 8) (98.9 ± 62.4 min vs 61.7 ± 17.6 min, P = 0.04), although the specimen size did not differ. CONCLUSION: Training in animal models could help endoscopists overcome the learning curve before starting ESD in humans.