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Although endoscopic submucosal dissection has been shown to be safe and effective for colorectal tumors, its clinical outcomes vary.The aim of this study is to assess the outcomes of endoscopic submucosal dissection according to clinical indications.This is a prospective, multicenter, single-arm study.The study was conducted at special hospitals for colorectal diseases and cancers.The study population included consecutive patients aged 20 to 80 years who underwent colorectal endoscopic submucosal dissection for 1) early colorectal cancer, 2) laterally spreading tumors ≥2 cm in diameter, and 3) submucosal tumors.Procedures were performed by experienced colonoscopists.The primary end points were en bloc and curative resection rates. En bloc resection was defined as endoscopic one-piece resection without tumor fragmentation. Curative resection was defined as en bloc resection and no pathologic requirement for additional surgery. Secondary end points included procedure time, complications, and hospital stay.Of 321 patients, 317 (98.8%) underwent en bloc resection and 231 (72.0%) underwent curative resection. The mean procedure time was 46.2 minutes. Mean hospital stay after the procedure was 3.1 days. Perforation occurred in 2 patients (0.6%), and bleeding occurred in 10 (3.1%) patients. All patients with complications were treated by endoscopic clipping or nonoperative management. Fifteen patients (4.7%) underwent additional radical surgery owing to the risks of lymph node metastasis. Although tumor size was smaller and procedure time shorter in the submucosal tumor group than in the laterally spreading tumor or early colorectal cancer group, there were no differences in clinical outcomes including en bloc and curative resection rates. Submucosal fibrosis was the only factor affecting endoscopic submucosal dissection procedure-related complications.Early outcomes in a limited population and the potential for selection bias were limitations of this study.Outcomes of colorectal endoscopic submucosal dissection were acceptable in selected patients, with no difference in outcomes according to clinical indications. Because submucosal fibrosis can increase complications, it should be minimized before endoscopic submucosal dissection.