Objective To study the therapeutic velue of endoscopic submucosal dissection (ESD) for colorectal tumors with different diameters. Methods Data of 210 cases which were treated with ESD for colorectal tumors at the Endoscopy Center, the Seventh Medical Center of PLA General Hospital from October 2012 to December 2015 were retrospctively analyzed. The lesions were divided into two groups according to different diameters (≥ 4.0 cm group and < 4.0 cm group) for comparative analysis of related factors. Results The mean procedure time of ESD for 210 colorectal tumor cases was 50.3 ± 42.7 min and the mean size of lesions was 7.98 ±10.84cm₂ . En bloc resection rate was 91.4%, R0 resection rate was 90.5%, and the curative resection rate was 88.6%. Perforation rate was 5.2% (11/210), and the late hemorrhage rate was 0.5% (1/210). Compared with lesions < 4.0 cm, those ≥4 cm required longer resection time (79.63±53.91 min vs 35.28±24.99 min; P<0.001); and the lesions were mainly located in the rectum (61.97%). LSTs were mainly mixed granular/nongranular type(54.93%); en bloc resection rate, complete resection rate and curative resection rate of the tumors ≥ 4.0 cm were all lower than those of tumors< 4.0 cm. The difference in complete resection rate was statistically significant (85.92% vs. 94.24%; P=0.041). The perforation rate (7.04%) was higher in ≥4.0 cm group, but the difference was not statistically significant. Conclusions ESD of colorectal tumors of ≥4.0 cm requires longer time with higher operation risk. Additionally, physicians should be more careful with non-rectal lesions.