The aim of this feasibility study was to evaluate the diagnostic accuracy of ultra-low-dose CT colonography using iterative reconstruction algorithms with reference to standard colonoscopy. Prior to this study, a phantom study was performed to investigate the optimal protocol for ultra-low-dose CT colonography. A total of 206 patients with average/high risk of colorectal cancer were recruited. After undergoing full bowel preparation, the patients were scanned in the prone and supine positions with the CT conditions set to 120kV, standard deviation 45 to 50, and an adaptive iterative reconstruction algorithm applied. Two expert readers read the images independently. The main outcome measures were the per-patient and per-polyp accuracies for the detection of polyps ≥ 10mm, with colonoscopy results as the reference standard. Two hundred patients (102 females, mean age 67.5years) underwent both ultra-low-dose CT colonography and colonoscopy on the same day. The mean radiation exposure dose was 0.64 ± 0.34mSv. On colonoscopy, 39 patients had 45 polyps ≥ 10mm (non-polypoid morphology 7), including 4 cancers. Per-patient sensitivity, specificity, and accuracy of CT colonography for polyps ≥ 10mm were 0.74, 0.96, and 0.92 for reader one, and 0.74, 0.99, and 0.94 for reader two, respectively. Per-polyp sensitivities for polyps ≥ 10mm were 0.73 for reader one and 0.71 for reader two. On subgroup analysis by morphology, non-polypoid polyps ≥ 10mm were not detected by both readers. Extreme ultra-low-dose CT colonography had an insufficient diagnostic performance for the detection of polyps ≥ 10mm, because it was unable to detect non-polypoid polyps. This study showed that the problem with ultra-low-dose CT colonography was the lack of detectability of small-size polyps, especially non-polypoid polyps. To use ultra-low-dose CT colonography clinically, it is necessary to resolve the problems identified by this study.