Despite its growing popularity, endoscopic submucosal dissection (ESD) for colorectal neoplasms is still technically challenging. The factors contributing to the failure of ESD are not yet comprehensively elucidated. Therefore, this systematic review was conducted to explore the potential risk factors associated with unsuccessful colorectal ESD.A comprehensive search of Medline and Embase databases was conducted to identify relevant publications from inception until March 14, 2023. Unsuccessful ESD was defined as cases involving incomplete resection or the occurrence of adverse events, such as perforation and delayed bleeding.Among the 2067 citations initially identified, a total of 23 cohort studies and 16 case-control studies met the inclusion criteria. Following meta-analyses, several significant risk factors for incomplete resection were identified, including lesion diameter ≥40 or 50 mm, right-side colonic location, deeper submucosal invasion, and severe fibrosis. Similarly, lesion diameter ≥40 or 50 mm and severe fibrosis emerged as risk factors for perforation. However, no individual factor was found to be statistically associated with delayed bleeding.This meta-analysis identified risk factors correlated with incomplete resection and adverse events following ESD. The findings provide valuable insights that can guide clinical decision-making, aiding gastroenterologists in accurately identifying high-risk individuals.Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.