OBJECTIVE Endoscopic mucosal resection (EMR) is the standard procedure for treatment of colorectal tumors. Endoscopic submucosal dissection (ESD) can be performed for resection of larger tumors, but has not been studied in the colorectum because of technical difficulties and complications. We compared outcomes and complications after resection of colorectal tumors larger than 20 mm diameter by ESD and EMR. METHODS We retrospectively studied 104 colorectal tumors treated with EMR from 1995 to 2004, and 85 colorectal tumors treated with ESD from 2005 to 2009. We compared the tumor location, shape, size, procedure time, en bloc resection rate, recurrence rate, and associated complications between the treatments. RESULTS Tumors treated with ESD were larger (31.6 ± 9.0 vs. 25.5 ± 6.8 mm, P<0.001), incurred a longer procedure time (87.2 ± 49.7 vs. 29.4 ± 26.1 min, P<0.001), had a higher en bloc resection rate [71 of 85 tumors (83.5%) vs. 50 of 104 tumors (48.1%), P<0.001], and had a lower recurrence rate [one of 84 tumors (1.2%) vs. 16 of 104 tumors (15.4%); P=0.002] compared with EMR. Perforation occurred in five (5.9%) cases after ESD and in none after EMR (P=0.04). Postoperative bleeding occurred in two (2.4%) and three (2.9%) cases after ESD and EMR (P=not significant), respectively. Although 11 of 16 cases with recurrence after EMR were cured by additional endoscopic treatment, three cases required surgery. The only recurrence after ESD was in one patient who developed perforation after snare EMR. CONCLUSIONS Despite its longer procedure time and higher perforation rate, ESD resulted in a higher en bloc resection rate and lower recurrence rate for larger colorectal tumors compared with EMR.