OBJECTIVE We sought to compare the performance of 3 computer-aided detection (CAD) polyp algorithms in computed tomography colonography (CTC) with fecal tagging. METHODS CTC data sets of 33 patients were retrospectively analysed by 3 different CAD systems: system 1, MedicSight; system 2, Colon CAD; and system 3, Polyp Enhanced View. The polyp database comprised 53 lesions, including 6 cases of colorectal cancer, and was established by consensus reading and comparison with colonoscopy. Lesions ranged from 6-40 mm, with 25 lesions larger than 10 mm in size. Detection and false-positive (FP) rates were calculated. RESULTS CAD systems 1 and 2 could be set to have varying sensitivities with higher FP rates for higher sensitivity levels. Sensitivities for system 1 ranged from 73%-94% for all lesions (78%-100% for lesions > or =10 mm) and, for system 2, from 64%-94% (78%-100% for lesions > or =10 mm). System 3 reached an overall sensitivity of 76% (100% for lesions > or =10 mm). The mean FP rate per patient ranged from 8-32 for system 1, from 1-8 for system 2, and was 5 for system 3. At the highest sensitivity level for all polyps (94%), system 2 showed a statistically significant lower FP rate compared with system 1 (P = .001). When analysing lesions > or =10 mm, system 3 had significantly fewer FPs than systems 1 and 2 (P < .012). CONCLUSIONS Standalone CTC-CAD analysis in the selected patient collective showed the 3 systems tested to have a variable but overall promising performance with respect to sensitivity and the FP rate.