Background and study aims: Endoscopic resection is the cornerstone of endoscopic treatment of esophageal high grade dysplasia or early cancer. Endoscopic resection is, however, a technically demanding procedure, which requires training and expertise. The aim of the current study was to prospectively evaluate efficacy and safety of the first 120 endoscopic resection procedures of early esophageal neoplasia performed by six endoscopists (20 endoscopic resections each) who were participating in an endoscopic resection training program. Patients and methods: The program consisted of four tri-monthly 1-day courses with lectures, live-demonstrations, hands-on training on anesthetized pigs, and one-on-one hands-on training days. Gastroenterologists from centers with multidisciplinary expertise in upper gastrointestinal oncology participated, together with an endoscopy nurse and a pathologist. Outcome measures were complete endoscopic removal of the target area and acute complications. Results: A total of 120 consecutive esophageal endoscopic resection procedures (85 ER-cap, 35 multiband mucosectomy [MBM]) were performed by six endoscopists: 109 in Barrett's esophagus, 11 for squamous neoplasia; 85 piecemeal endoscopic resections (median 3 specimens, interquartile range 2-4 specimens). Complete endoscopic removal was achieved in 111/120 cases (92.5%). Six perforations occurred (5.0%): five were effectively treated endoscopically (clips, covered stent), and one patient underwen Conclusion: In this intense, structured training program, the first 120 esophageal endoscopic resections performed by six participants were associated with a 5.0% perforation rate. Although perforations were adequately managed, performing 20 endoscopic resections may not be sufficient to reach the peak of the learning curve in endoscopic resection.