OBJECTIVES: The majority of recent cost-effectiveness reviews concluded that computerized tomographic colonography (CTC) is not a cost-effective Colorectal Cancer (CRC) screening strategy yet. The objective of this review is to examine cost-effectiveness of CTC versus optical colonoscopy (COL) for CRC screening and identify the main drivers influencing cost-effectiveness due to the emergence of new research. METHODS: A systematic review was conducted for cost-effectiveness studies comparing CTC and COL as a screening tool and providing outcomes in life-years saved, published between January 2006 and November 2012. The following databases were searched: PubMed, Science Direct, Cochrane Library and the York Centre for Reviews and Dissemination databases. The search methodology was in line with PRISMA guidelines, including the use of the PICOS review system. RESULTS: Nine studies were included in the review. There was considerable heterogeneity in modelling complexity and methodology. Different model assumptions and inputs had large effects on resulting cost-effectiveness. The most important assumptions that influenced the cost-effectiveness of CTC and COL were related to CTC threshold-based reporting of polyps, CTC cost, CTC sensitivity for large polyps, natural history of adenoma transition to cancer and importantly, adherence. CTC was found to be cost-effective in three studies, assuming the most favourable scenario. CONCLUSIONS: CTC has the potential to be a cost-effective CRC screening strategy when compared to COL. There is a strong need for a differential consideration of patient adherence and compliance to CTC and COL. Recent research shows that laxative-free CTC screening has the potential to become a viable alternative screening method for CRC as it can improve patient uptake of screening. This project is supported by the German Federal Ministry of Education and Research (BMBF) as part of the National Cluster of Excellence ‚Medical Technologies - Medical Valley EMN’ (Project grant No. 13EX1013B).