BACKGROUND: There is no evidence demonstrating the feasibility of colorectal natural orifice transluminal endoscopic surgery (NOTES) resection with currently available endoscopic instrumentation. OBJECTIVE: This study aimed to evaluate the responsiveness of surgical endoscopists to simulated transanal NOTES sigmoidectomy training. DESIGN: Participants were trained in simulated NOTES sigmoidectomy by using disposable abdominal trays with tattooed sigmoid cancer in a hybrid simulator. SETTING: Endoscopy simulation laboratory in a university hospital. INTERVENTIONS: NOTES sigmoidectomy included 8 steps performed transanally with 2 colonoscopes, endoscopic scissors, and clip applier: (1) colonoscopic viscerotomy with a balloon; (2) retroperitoneal dissection; (3) left ureter identification, inferior mesenteric vessels division; (4) colonoscopy; (5) splenic flexure mobilization; (6) left side of the colon/rectal mobilization; (7) transanal specimen transection; (8) extracorporeal colorectal anastomosis. MAIN OUTCOME MEASUREMENTS: Responsiveness was defined as a change in performance over time and assessed comparing baseline testing with unmentored final testing. Content-valid measures included the length of the specimen, the distance of the anastomosis from the anal verge, and the proximal and distal resection margins and operating time (minutes). RESULTS: Four participants performed 21 resections. Tumor distance from the anal verge was 29.2 cm (range 26-2.5 cm). Operating time overall (127.5 vs 74 minutes, P = .068), viscerotomy (17.5 vs 9 minutes, P = .197), colonoscopy (4.5 vs 3.5 minutes, P = .655), flexure mobilization (19.5 vs 10 minutes, P = .144), colon mobilization (20 vs 14.5 minutes, P = .461), specimen extraction (9.5 vs 8.5 minutes, P = .465), and anastomosis (14 vs 11 minutes, P = .715) times improved. LIMITATIONS: Ceiling effects because of fixed anatomy. CONCLUSIONS: Simulated NOTES sigmoidectomy training affected responsiveness of surgical endoscopists with a 42% reduction in operating time.