To determine the positive predictive value (PPV) for polyps detected at CT colonography (CTC). Assessment of 739 colorectal lesions >or=6 mm detected prospectively at CTC screening in 479 patients was performed. By-polyp PPV was analyzed according to small (6-9 mm) versus large (>or=10 mm) size; morphology (sessile/pedunculated/flat); diagnostic confidence level (3 = most confident, 1 = least confident); and histology. By-patient PPV was analyzed at various polyp size thresholds. By-polyp PPV for CTC-detected lesions >or=6 mm, 6-9 mm, and >or=10 mm was 91.6% (677/739), 90.1% (410/451), and 92.7% (267/288), respectively (p = 0.4). By-polyp PPV according to sessile, pedunculated, flat, and mass-like morphology was 92.5% (441/477), 96.5% (139/144), 77.7% (73/94), and 97.6% (40/41), respectively (p or=6 mm was 92% for CTC screening. Increased diagnostic confidence and polypoid (non-flat) morphology correlated with a higher PPV, whereas small versus large polyp size had very little effect.