Background: There is increasing discussion whether colorectal cancer (CRC) screening guidelines should be individualized by sex and race. Objectives: To determine individualized colonoscopic screening guidelines by sex and race for the average-risk population and to compare the cost-effectiveness of this approach with that of uniform guidelines for all. Design: We used the MISCAN-Colon microsimulation model to estimate life expectancy and lifetime CRC screening and treatment costs in a U.S. cohort of black and white men and women at average risk for CRC. We compared the base-case strategy of no screening and 3 competing colonoscopy strategies: (1) the currently recommended "uniform 10-yearly colonoscopy from age 50 years," (2) a shorter interval "uniform 8-yearly colonoscopy from age 51 years," and (3) "individualized screening according to sex and race.". Results: The base-case strategy of no screening was the least expensive, yet least effective. The uniform 10-yearly colonoscopy strategy was dominated. The uniform 8-yearly colonoscopy and individualized strategies both increased life expectancy by 0.0433 to 0.0435 years per individual, at a cost of $15,565 to$15,837 per life-year gained. In the individualized strategy, blacks began screening 6 years earlier, with a 1-year shorter interval compared with whites. The individualized policies were essentially the same for men and women, because the higher CRC risk in men was offset by their shorter life expectancy. The results were robust for changes in model assumptions. Conclusions: The improvements in costs and effects of individualizing CRC screening on a population level were only marginal. Individualized guidelines, however, could contribute to decreasing disparities between blacks and whites. The acceptability and feasibility of individualized guidelines, therefore, should be explored.