OLORECTAL CANCER (CRC) accounts for approximately 210 000 deaths each year in Europe. 1 The majority of CRCs arise within adenomatous polyps, 2 and polypectomy is associated with a reduction in CRC incidence and mortality. 3 The target lesions in mass screening programs are advanced adenomas, which harbor the greatest cancer risk, and early stage CRC, 4 but adherence to screening procedures remains suboptimal. 5,6 Computed tomographic (CT) colonography has been shown to be sufficiently accurate in detecting colorectal neoplasia. 7,8 Less invasive and better tolerated than colonoscopy, 9,10 CT colo-nography is now considered a valid alternative for CRC screening in the general population. 11 Individuals with first-degree family history of advanced colorectal neoplasia, those who have had resection of co-For editorial comment see p 2498. Context Computed tomographic (CT) colonography has been recognized as an alternative for colorectal cancer (CRC) screening in average-risk individuals, but less information is available on its performance in individuals at increased risk of CRC. Objective To assess the accuracy of CT colonography in detecting advanced colorectal neoplasia in asymptomatic individuals at increased risk of CRC using unblinded colonoscopy as the reference standard. Design, Setting, and Participants This was a multicenter, cross-sectional study. Individuals at increased risk of CRC due to either family history of advanced neoplasia in first-degree relatives, personal history of colorectal adenomas, or positive results from fecal occult blood tests (FOBTs) were recruited in 11 Italian centers and 1 Belgian center between December 2004 and May 2007. Each participant underwent CT colonography followed by colonoscopy on the same day. Main Outcome Measures Sensitivity and specificity of CT colonography in detecting individuals with advanced neoplasia (ie, advanced adenoma or CRC) 6 mm or larger. Results Of 1103 participants, 937 were included in the final analysis: 373 cases in the family-history group, 343 in the group with personal history of adenomas, and 221 in the FOBT-positive group. Overall, CT colonography identified 151 of 177 participants with advanced neoplasia 6 mm or larger (sensitivity, 85.3%; 95% confidence interval [CI], 79.0%-90.0%) and correctly classified results as negative for 667 of 760 participants without such lesions (specificity, 87.8%; 95% CI, 85.2%-90.0%). The positive and negative predictive values were 61.9% (95% CI, 55.4%-68.0%) and 96.3% (95% CI, 94.6%-97.5%), respectively; after group stratification, a significantly lower negative predictive value was found for the FOBT-positive group (84.9%; 95% CI, 76.2%-91.3%; PϽ.001). Conclusions In a group of persons at increased risk for CRC, CT colonography compared with colonoscopy resulted in a negative predictive value of 96.3% overall. When limited to FOBT-positive persons, the negative predictive value was 84.9%.