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Colorectal laterally spreading tumors (LSTs) are large and flat elevated neoplasms with diameters of at least 10 mm. Endoscopic resection of LSTs, with their large size and broad base, is difficult and dangerous compared with the resection of polypoid neoplasms. This study aimed to determine the risk factors for procedure-related complications including bleeding and perforation after endoscopic resection of LSTs.Patients with colorectal LST undergoing endoscopic resection at 5 university hospitals in Honam Province of South Korea were enrolled, and their records about patients, lesions, and procedure parameters associated with the occurrence of complications were reviewed retrospectively. Logistic regression analysis was performed to identify risk factors for complications.The frequency of comorbidities in bleeding group was significantly higher than in the no bleeding group. The frequency of bleeding was significantly higher in lesions with adenocarcinoma than in lesions with low or high-grade dysplasia. The frequency of bleeding was significantly higher in piecemeal resection than in en bloc resection. The frequency of perforation was significantly higher in endoscopic mucosal resection-precutting (EMR-P) than in endoscopic mucosal resection (EMR) or endoscopic submucosal dissection. The mean procedure duration was significantly longer in the perforation group than in the no perforation group. On multivariate analysis, patient comorbidity and histologic grade of the lesion were significant independent risk factors for bleeding, whereas EMR-P was a significant independent risk factor for perforation after endoscopic resection.This study demonstrated that patient comorbidity and histologic grade of lesion were significant independent risk factors for bleeding, and EMR-P was a significant independent risk factor for perforation after endoscopic resection of colorectal LSTs.