Purpose: To compare the diagnostic yields of a radiologist and trained technologists in the detection of advanced neoplasia within a population-based computed tomographic (CT) colonography screening program. Materials and Methods: Ethical approval was obtained from the Dutch Health Council, and written informed consent was obtained from all participants. Nine hundred eighty-two participants (507 men, 475 women) underwent low-dose CT colonography after noncathartic bowel preparation (iodine tagging) between July 13, 2009, and January 21, 2011. Each scan was evaluated by one of three experienced radiologists (≥800 examinations) by using primary two-dimensional (2D) reading followed by secondary computer-aided detection (CAD) and by two of four trained technologists (≥200 examinations, with colonoscopic verification) by using primary 2D reading followed by three-dimensional analysis and CAD. Immediate colonoscopy was recommended for participants with lesions measuring at least 10 mm, and surveillance was recommended for participants with lesions measuring 6-9 mm. Consensus between technologists was achieved in case of discordant recommendations. Detection of advanced neoplasia (classified by a pathologist) was defined as a true-positive (TP) finding. Relative TP and false-positive (FP) fractions were calculated along with 95% confidence intervals (CIs). Results: Overall, 96 of the 982 participants were referred for colonoscopy and 104 were scheduled for surveillance. Sixty of 84 participants (71%) referred for colonoscopy by the radiologist had advanced neoplasia, compared with 55 of 64 participants (86%) referred by two technologists. Both the radiologist and technologists detected all colorectal cancers (n = 5). The relative TP fraction (for technologists vs radiologist) for advanced neoplasia was 0.92 (95% CI: 0.78, 1.07), and the relative FP fraction was 0.38 (95% CI: 0.21, 0.67). Conclusion: Two technologists serving as a primary reader of CT colonographic images can achieve a comparable sensitivity to that of a radiologist for the detection of advanced neoplasia, with far fewer FP referrals for colonoscopy.