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Colorectal cancer (CRC) screening uptake in the Veterans Health Administration (VA) has been reported to be higher than the US general population, but CRC remains a prevalent cancer within the VA system. To examine CRC predictors and the extent to which the conventional definition of up-to-date screening applies to the population, we conducted a case-control study using VA data from 2012 to 2018. We classified patients into 5 categories: up-to-date or not up-to-date average-risk patients aged 50 to 75 (Categories 1 and 2), up-to-date or not up-to-date average-risk patients aged <50 or >75 (Categories 3 and 4), and high-risk patients (Category 5). Each CRC case was matched by age, sex, and facility with 4 controls. We performed multivariable conditional logistic regression, adjusting for race and ethnicity, diabetes, obesity, and alcohol use. Among 3714 CRC cases identified, Category 4 (odds ratio [OR] 1.40, 95% CI 1.11-1.78) and Category 5 (OR 6.23, 95% CI 5.06-7.66) patients had a higher risk of CRC compared to Category 1 patients. Compared with White patients, Black patients had a higher risk (OR 1.54, 95% CI 1.37-1.73). Diabetes (OR 1.65, 95% CI 1.51-1.81) and alcohol use disorder (OR 1.53, 95% CI 1.35-1.73) were also associated with CRC. Most CRC cases occurred in individuals aged 50 to 75, but 12.5% occurred in persons who were outside of this age range or had high-risk personal or family history. The conventional measure of CRC screening, focused on average-risk individuals aged 50 to 75, does not reflect screening status in an important minority of CRC patients.