Rationale And Objectives: Multiple trials have documented wide interobserver variability between radiologists interpreting computed tomography colonography (CTC) exams. We sought to determine if nonradiologists could learn to interpret intraluminal findings at CTC with a high degree of sensitivity to determine if they could play a role as second readers in interpreting CTC exams.Materials And Methods: Seven nonradiologists (five medical students, two radiologic technologists) undertook self-directed CTC training using a teaching file of 50 cases; thereafter, each reader blindly interpreted 50 cases with colonoscopic correlation (30 positive, 20 negative). Results were compared with a previously studied cohort of radiologists. The two technologists additionally repeated the exam after 6 weeks of clinical experience.Results: The sensitivity of nonradiologists for small (5-9 mm) polyps, large (>9 mm) lesions, and cancers was similar to that of radiologists (0.45 versus 0.63, 0.74 versus 0.71, and 0.80 versus 0.88, respectively). After 6 weeks of clinical experience as second readers, the accuracy of one technologist significantly improved (from 74% to 90%, P = .008), whereas accuracy of the other tended toward improvement (from 74% to 86%%, P = .25). Nonradiologists detected, on average, 6/36 additional polyps (17%) missed by any radiologist, and the sensitivity of 5/7 nonradiologists was significantly greater than at least one of the radiologists (P = .05).Conclusion: Nonradiologists can perform similarly to radiologists in interpreting intraluminal findings at CTC, with nonradiologist performance improving even after experience with more than 100 cases. Skilled nonradiologists may play a vital role as a second reader of intraluminal findings or by performing quality control of examinations before patient dismissal.