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Colorectal cancer (CRC) screening with colonoscopy is commonly used in patients who are candidates for liver transplantation. We initiated this study to define the risk-benefit ratio of performing screening colonoscopy in this population. A retrospective observational study of all consecutive patients undergoing colonoscopy during pre-liver transplantation screening between 2004 and 2017 was conducted. Endoscopic and pathological findings and clinical events potentially related to the colonoscopy in the 30 days after the procedure were registered and compared with a 30-day inpatient control time frame. A total of 858 colonoscopies were performed in 808 patients (65% male; median age, 55 years [interquartile range (IQR), 47-62]; median model for end-stage liver disease (MELD) score, 15 [IQR, 11-18]). CRC was found in 2 patients (0.2%), and advanced adenomas were found in 44 patients (5.4%). The only independent risk factor for an advanced neoplasm was age (odds ratio, 1.072 per year; 95% confidence interval, 1.031-1.115; P0.001). During the 30-day postprocedure period, 178 clinical events occurred in 128 patients compared with 101 clinical events in 72 patients in the control time frames (P0.001). After colonoscopy, there was a significantly increased risk for renal failure (P = 0.001) and gastrointestinal (GI) bleeding (P = 0.023). Presence of ascites and MELD score were identified as independent risk factors for acute renal failure and GI bleeding. During the study observation period, 53.5% of the screened population actually underwent liver transplantation. Conclusion: CRC screening in pre-liver transplantation patients is associated with a relatively low prevalence of CRC and an increased risk of postcolonoscopy complications such as acute renal failure and GI bleeding, especially in patients with advanced liver disease. Because the risk-benefit ratio of standard performance of a screening colonoscopy in this population appears questionable, alternative screening strategies should be considered.