OBJECTIVE: CT colonography studies to date have used a standard CT algorithm. To determine whether nonstandard algorithms may result in better performance of CT colonography, we conducted a prospective, blinded-observer study of the effect of the reconstruction algorithm on the conspicuity of colonic polyps and folds. SUBJECTS AND METHODS: CT colonography of patients with proven polyps, masses, or polypoid folds was performed on an MDCT scanner, and the images were reconstructed using the standard, soft, lung, and detail algorithms. Two experiments were performed. The first used four patient data sets of a short segment of colon (30-60 images), each reconstructed using all four algorithms and then viewed on a workstation in a four-on-one format that allowed all four reconstructions to be viewed simultaneously. The second used six sets of cut-film images (four or eight images each); images within each set differed only in the reconstruction algorithm used to generate them (eight-image sets were prepared with two different level settings). Twenty-one reviewers with varying levels of experience who were unaware of the purpose of the study were asked to rank the images within each set according to their value in the detection of either polyps or masses. RESULTS: Reviewers showed statistically significant differences in preference for the four algorithms (p = 0.037 in the computer-based experiment; for the cut-film experiment, p = 0.029 for the four-image sets and p = 0.041 for the eight-image sets). In the computer-based experiment, reviewers preferred the detail algorithm to the standard algorithm with an estimated probability of 0.67 (95% confidence interval [CI], 0.57-0.75) and the soft algorithm over the standard algorithm with an estimated probability of 0.59 (95% CI, 0.51-0.66). However, reviewers with the most experience (having interpreted at least 250 cases) preferred the soft algorithm over the standard algorithm by the same two-to-one margin as observed for the detail algorithm. In contrast, the standard and detail algorithms were ranked similarly in the cut-film experiment, with the soft and lung algorithms ranked worst. CONCLUSION: To our knowledge, ours is the first observer study on the effect of the reconstruction algorithm on conspicuity of folds and polyps in CT colonography. Our results indicate significant differences in the reconstruction algorithms, with the soft and detail algorithms being preferred over the standard algorithm by experienced reviewers when interpreting images on a workstation. These results indicate the need for further research into the effect of reconstruction algorithms on CT colonography.