Post-colonoscopy colorectal cancer (PCCRC) is CRC diagnosed after a colonoscopy in which no cancer was found. A consensus article from the World Endoscopy Organization (WEO) proposed an approach for investigating and categorizing PCCRCs detected within 4 years of a colonoscopy. We aimed to identify cases of PCCRC and the factors that cause them, test the WEO system of categorization, quantify the proportion of avoidable PCCRCs, and propose a target rate for PCCRCs detected within 3 years of a colonoscopy that did not detect CRC. We performed a retrospective analysis of 107 PCCRCs identified at a single medical center in England from Jan 1, 2010 through December 31, 2017 using coding and endoscopy data. For each case, we reviewed clinical, pathology, radiology, and endoscopy findings. Using the WEO recommendations, we performed a root cause analysis of each case, categorizing lesions as: possible missed lesion, prior examination adequate; possible missed lesion, prior examination inadequate; detected lesion, not resected; or likely incomplete resection of previously identified lesion. We determined whether PCCRCs could be attributed to the colonoscopist for technical or decision-making reasons, and whether the PCCRC was avoidable or unavoidable, based on the WEO categorization and size of tumor. The endoscopy reporting system provided performance data for individual endoscopists. Of the PCCRCs identified, 43% were in high-risk patients (those with inflammatory bowel disease, previous CRC, previous multiple large polyps or hereditary cancer syndromes) and 66% were located distal to the hepatic flexure. There was no correlation between post-colonoscopy colorectal tumor size and time to diagnosis after index colonoscopy. Bowel preparation was poor in 19% of index colonoscopies, and only 36% of complete colonoscopies had adequate photo documentation of completion. Development of 73% of PCCRCs was determined to be affected by technical endoscopic factors, 17% of PCCRCs by administrative factors (follow-up procedures delayed/not booked by administrative staff), and 27% of PCCRCs by decision-making factors. Twenty-seven percent of PCCRCs were categorized as possible missed lesion, prior examination adequate; 58% as possible missed lesion, prior examination inadequate; 8% as detected lesion, not resected; and 7% as incomplete resection of previously observed lesion; 89% were deemed to be avoidable. In a retrospective analysis of PCCRCs, using the WEO system of categorization, we found 43% to occur in high-risk patients; this might be reduced with more vigilant surveillance. Measures are needed to reduce technical, decision-making and administrative factors. We found that 89% of PCCRCs may be avoidable. If half of avoidable PCCRCs could be prevented, the target rate of 2% for the PCCRC-3y benchmark would be achievable. Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.