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Colonoscopy is effective for colorectal cancer (CRC) prevention, yet patients may develop CRC despite adhering to screening/surveillance intervals. There are limited data on predictive factors associated with these postcolonoscopy CRCs (PCCRCs). We aimed to measure PCCRC rates and identify risk factors for PCCRC.We performed a case-control study, comparing patients with PCCRCs to spontaneous CRCs diagnosed during a 12.5-year period at an academic medical center. PCCRCs were defined as CRCs diagnosed in between guideline-recommended screening/surveillance intervals.During the 12.5-year period, of 1266 CRCs diagnosed, 122 (10%) were PCCRCs. 70% of PCCRCs were diagnosed within 5 years of a prior colonoscopy. There was an increasing trend for PCCRC rates in recent years [odds ratio (OR), 2.78; 95% confidence interval (CI), 1.51-5.09], with PCCRCs comprising 13.6% of cancers diagnosed in 2016 as compared with 5.7% of cancers diagnosed in 2005. Older age (OR per year, 1.02; 95% CI, 1.01-1.04), proximal colonic location (OR, 1.99; 95% CI, 1.20-3.33) and early stage (OR, 2.57; 95% CI, 1.34-4.95) were associated with PCCRCs. In total, 41% of PCCRCs were diagnosed by a different physician from the physician who did the prior colonoscopy, and 42% of physicians did not diagnose any of their PCCRC cases.PCCRC rates are rising in recent years, likely reflecting the widespread adoption of colonoscopy as a primary screening tool, and are more common in older patients and those with proximal, early-stage tumors. The finding that a large proportion of PCCRCs are diagnosed by a different physician raises the concern that physicians are unaware of their own patients’ PCCRCs.