Objective To evaluate the outcome of endoscopic submucosal dissection (ESD) of colorectal tumors, and to analyze the factors affecting the therapeutic efficacy of ESD. Methods Clinical data of patients with colorectal tumors who were treated with ESD in Department of Gastroenterology in Beijing Hospital from November 2016 to December 2019 were reviewed. A total of 82 patients with pathologically confirmed colorectal adenoma or carcinoma of diameter ≥20 mm were included. The clinical features, ESD and pathological outcomes of the patients were analyzed. Results All 82 lesions were single, with the mean diameter of 29.72±10.74 mm. Lesions were divided into the laterally spreading tumors (LST), mainly located in the ascending colon and ileocecal region (47.8%, 22 / 46) and the protruding colorectal tumors, mainly located in the left colon, 52.8% (19 / 36) of which were located in the sigmoid colon. The overall resection rate was 81.7%(67/82) and the curative resection rate was 72.0%(59/82). The incidences of bleeding and perforation were 2.4%(2/82) and 1.2%(1/82), respectively. The curative resection rates [91.4%(32/35), 63.6%(7/11) and 55.6%(20/36), P=0.003] and surgical operation rates (8.6%, 18.2% and 36.1%, P=0.010) of LST-G, LST-NG and protruding colorectal tumors were significantly different. Multivariate regression analysis showed that protruding colorectal tumor (OR=3.396, 95%CI:1.014-11.374, P=0.047) and submucosal severe fibrosis (F2 type) (OR=5.508, 95%CI:2.216-13.692, P=0.001) were independent risk factors for non-curative ESD resection of colorectal tumors. Conclusion ESD is effective and safe for colorectal tumors of diameter ≥ 20 mm. However, there are some differences in the rate of submucosal invasion and treatment outcome among different types of lesions. The risk factors for non-curative resection are protruding tumors and severe submucosal fibrosis.