Background & Aims: Computerized tomography colonography (CTC) is a highly accurate test for the detection of colorectal polyps and cancers and has been proposed as a potential alternative to colonoscopy. Bowel cancer screening using fecal occult blood testing (FOBT) and follow-up diagnostic colonoscopy is an effective intervention that currently is being implemented in screening programs internationally. Because of high false-positive rates for FOBT, concerns have been raised about patient uptake and access to colonoscopy services. This study assessed the value of CTC as an alternative to colonoscopy in FOBT-positive individuals. Methods: A systematic review of studies comparing the accuracy of CTC and colonoscopy for the detection of lesions 10 mm or greater and cancers in nonscreening populations was conducted. A modeled economic analysis was undertaken to assess cost per life-year saved. Results: Five eligible studies were identified. Pooled sensitivity and specificity for the detection of lesions 10 mm or greater were 63% (95% confidence interval [CI], 55%–71%) and 95% (95% CI, 94%–97%) for CTC, and 95% (95% CI, 90%–98%) and 99.8% (95% CI, 99.5%–100%) for colonoscopy, respectively (3 studies). Pooled sensitivity and specificity for the detection of cancer were 89% (95% CI, 70%–98%) and 97% (95% CI, 95%–98%) for CTC, and 96% (95% CI, 80%–100%) and 99.7% (95% CI, 99%–100%) for colonoscopy, respectively (3 studies). The base case economic analysis showed that CTC is less effective and more costly than colonoscopy. At a low prevalence of polyps, sensitivity analysis found CTC was less effective and less costly than colonoscopy; if CTC was more sensitive than colonoscopy, CTC was more effective, at higher cost. Conclusions: Overall, CTC appears less accurate, less effective, and potentially more costly than colonoscopy in individuals with a positive FOBT.