BACKGROUND Although endoscopic submucosal tunnel dissection has been used for the resection of esophageal and stomach neoplastic lesions, there are still no reports about large superficial rectal neoplastic lesions. Compared with esophageal and stomach endoscopic submucosal dissection, the dissection of large superficial rectal neoplastic lesions is more difficult because of the flimsy bowel wall with abundant vasculature in the submucosal region, which results in poor endoscopic maneuverability and serious complications, such as bleeding and perforation. OBJECTIVE The study aimed to assess the efficacy and safety of endoscopic submucosal tunnel dissection for large superficial rectal neoplastic lesions over 5 to 24 months in selected patients. METHODS This was a prospective, single-center evaluation. METHODS The study was conducted at a digestive endoscopic center. METHODS Patients with large superficial rectal neoplastic lesions were included. METHODS Endoscopic submucosal tunnel dissection was performed in all of the patients with large, superficial rectal neoplastic lesions. The submucosal tunnel was created via a submucosal incision from the anal incision to the oral incision. Next, tunnel wall resection was performed to completely remove the lesion. METHODS Dissection speed, complications, and recurrence rate were measured. RESULTS A total of 19 patients, including 13 men and 6 women, with an average age of 60.1 ± 12.2 years (range, 34.0-75.0 y) underwent endoscopic submucosal tunnel dissection. The average size of lesions was 17.54 ± 13.47 cm. The mean operative time was 84.84 ± 53.49 minutes, and the operating speed was 21.01 ± 9.00 mm/min. En bloc resections with negative basal margins were achieved in all cases without serious intraoperative complications. No recurrence was observed in any patient within 5 to 24 months after the operations. CONCLUSIONS This was a single-center study. CONCLUSIONS Endoscopic submucosal tunnel dissection is feasible, safe, and effective for the treatment of large, superficial rectal neoplastic lesions in selected patients. See Video Abstract at http://links.lww.com/DCR/A321.