Objective We aimed to investigate the clinical outcomes of endoscopic submucosal dissection (ESD) for the treatment of colorectal laterally spreading tumors (LSTs) and the factors related to technical difficulty. Methods Consecutive patients who underwent ESD for colorectal LSTs between June 2013 and January 2019 were retrospectively included. Factors associated with difficult ESD procedures (defined as conversion to piecemeal resection or discontinuation of endoscopic procedure), and dissection with a slow speed (<8 mm(2)/min), were determined using the logistic regression analysis. Results A total of 325 patients with 342 colorectal LSTs (median size 20.0 mm) were enrolled. The proportions of granular (LST-G) and non-granular LST (LST-NG) were 62.9% and 37.1%, respectively. The overall en bloc and complete resection rates were 89.8% and 81.9%, respectively. The endoscopic procedure was discontinued in four lesions (1.2%), and 31 (9.1%) converted to piecemeal resection because of technical difficulty. Using multivariate analysis, positive non-lifting sign (odds ratio [OR] 19.9, P < 0.001), tumor size >= 20 mm (OR 10.0, P < 0.001), and less experienced endoscopists (OR 3.7, P = 0.005) were independent factors for technically difficult procedure. Positive non-lifting sign (OR 3.7, P = 0.004), lesion size <20 mm (OR 3.7, P < 0.001), LST-NG type (OR 1.8, P = 0.034), and less colorectal ESD experience (OR 1.9, P = 0.016) were independent factors of slow-speed dissection. Conclusions ESD was feasible and safe for treating colorectal LSTs. Positive non-lifting sign and tumor >= 20 mm indicated difficult ESD procedures. Technical failure was more likely to occur in lesions resected by less-experienced endoscopists. Dissection speed might be improved with more experienced operators.