The clinical outcomes for endoscopic submucosal dissection (ESD), a novel endoluminal surgery for gastrointestinal neoplasm in the colorectum, are reported. ESD was performed on 186 consecutive patients with 200 colorectal epithelial neoplasms who had preoperative diagnoses of mucosal or slight submucosally invasive neoplasms. In addition, these could be of large size, with submucosal fibrosis, or located on an intestinal fold. The therapeutic efficacy and safety were assessed. The targeted lesions consisted of 102 adenomas, 72 noninvasive carcinomas, and 26 invasive carcinomas. Seven lesions (3.5%) were histologically considered to be at substantial risk for nodal metastasis after ESD. The rate of en bloc resection was 91.5% (183/200), and en bloc resection with tumor-free lateral/basal margins (R0 resection) was 70.5% (141/200). Two lesions (1%) required emergency colonoscopies as a result of hematochezia after ESD. Eleven (5.5%) immediate perforations that occurred during ESD were successfully managed conservatively, but 1 (0.5%) delayed perforation required laparotomy. Two multiple-piece resections of 111 tumors (1.8%), which were successfully followed by colonoscopy (median follow-up, 18 months; range, 12-60 months), were found as locally recurrent tumors 2 and 21 months after ESD. No lymph node or distant metastasis was detected in 77 patients with noninvasive or invasive carcinoma (median follow-up, 24 months; range, 6-74 months). ESD is applicable in the colorectum with promising results. However, when considering the risks and benefits, piecemeal endoscopic resection or colorectal resection might be more appropriate for some subgroups of large flat neoplasms or those with submucosal fibrosis.