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Purpose: To prospectively evaluate the sensitivity and specificity of computed tomographic (CT) colonography with limited bowel preparation for the depiction of colonic polyps, by using colonoscopy as the reference standard., Materials and Methods: Institutional review board approval and written informed consent were obtained. Patients at increased risk for colorectal cancer underwent CT colonography after fecal tagging, which consisted of 80 mL of barium sulfate and 180 mL of diatrizoate meglumine. Bisacodyl was added for stool softening. A radiologist and a research fellow evaluated all data independently by using a primary two-dimensional approach. Discrepant findings for lesions 6 mm or larger in diameter were solved with consensus. Segmental unblinding was performed. Per-patient sensitivity and specificity, per-polyp sensitivity, and number of false-positive findings were found (for lesions > or = 6 mm and > or = 10 mm in diameter). Per-patient sensitivities (blinded colonoscopy vs CT colonography) were tested for significance with McNemar statistics. Interobserver variability was analyzed per segment (prevalence-adjusted bias-adjusted kappa values [kappa(p)])., Results: One hundred fourteen of 168 patients (105 men, 63 women; mean age, 56 years) had polyps, with 56 polyps 6 mm or larger and 17 polyps 10 mm or larger. Per-patient sensitivities were not significantly different for CT colonography (consensus reading) and colonoscopy (P > or = .070). Sensitivity of CT colonography for patients with lesions 6 mm or larger and 10 mm or larger was 76% and 82%, respectively, and specificity of CT colonography was 79% and 97%, respectively. Blinded colonoscopy depicted 91% (lesions > or = 6 mm) and 88% (lesions > or = 10 mm) of disease in patients. Per-polyp sensitivity for CT colonography was 70% (lesions > or = 6 mm) and 82% (lesions > or = 10 mm). Number of false-positive findings was 42 (lesions > or = 6 mm) and six (lesions > or = 10 mm). kappa(p) Was 0.88 (lesions > or = 6 mm) and 0.96 (lesions > or = 10 mm)., Conclusion: CT colonography with limited bowel preparation has a sensitivity of 82% and specificity of 97% for patients with polyps 10 mm or larger.