The costs of computed tomographic colonography (CTC) are not yet established for screening use. In our study, we estimated the threshold costs for which CTC screening would be a cost-effective alternative to colonoscopy for colorectal cancer (CRC) screening in the general population. We used the MISCAN-colon microsimulation model to estimate the costs and life-years gained of screening persons aged 50–80 years for 4 screening strategies: (i) optical colonoscopy; and CTC with referral to optical colonoscopy of (ii) any suspected polyp; (iii) a suspected polyp ≥6 mm and (iv) a suspected polyp ≥10 mm. For each of the 4 strategies, screen intervals of 5, 10, 15 and 20 years were considered. Subsequently, for each CTC strategy and interval, the threshold costs of CTC were calculated. We performed a sensitivity analysis to assess the effect of uncertain model parameters on the threshold costs. With equal costs ($662), optical colonoscopy dominated CTC screening. For CTC to gain similar life-years as colonoscopy screening every 10 years, it should be offered every 5 years with referral of polyps ≥6 mm. For this strategy to be as cost-effective as colonoscopy screening, the costs must not exceed $285 or 43% of colonoscopy costs (range in sensitivity analysis: 39–47%). With 25% higher adherence than colonoscopy, CTC threshold costs could be 71% of colonoscopy costs. Our estimate of 43% is considerably lower than previous estimates in literature, because previous studies only compared CTC screening to 10-yearly colonoscopy, where we compared to different intervals of colonoscopy screening. © 2008 Wiley-Liss, Inc.