The adoption of colorectal endoscopic submucosal dissection (ESD) is still limited in the West. A recent randomized trial showed ESD is more effective and only slightly riskier than piecemeal endoscopic mucosal resection (EMR); reproducibility outside expert centers was questioned. We evaluated the results according to the annual case volume in a multicentric prospective cohort. Between 09/2019 and 09/2022, colorectal ESD was consecutively performed at 13 participating centers classified as low-volume (LV), middle-volume (MV), and high-volume (HV). The main procedural outcomes were assessed. Multivariate and propensity score matching (PSM) analyses were performed. 3770 ESDs were included. HV centers treated larger and more often colonic lesions than MV and LV centers. En bloc, R0 and curative resection rates were 95.2%, 87.4%, and 83.2%, respectively, and were higher at HV than at MV and LV centers. HV centers achieved also a faster dissection speed. Delayed bleeding and surgery for complications rates were 5.4% and 0.8%, respectively, without significant differences. The perforation rate (overall: 9%) was higher at MV than at LV and HV centers. Lesion characteristics, but not volume center, were independently associated with both R1 resection and perforation. However, after PSM, R0 rates were significantly higher at HV than at LV centers, and perforation rates were significantly higher at MV than at HV centers. Colorectal ESD can be successfully implemented in the West, even in nonexpert centers. However, difficult lesions must still be referred to experts.