OBJECTIVES In Canada, colorectal cancer (CRC) screening is recommended for average-risk individuals age 50 - 75. A variety of options are available for screening those at average risk for CRC, including stool-based tests (such as fecal occult blood test (FOBT), fecal immunochemical tests (FITs), and fecal DNA), radiological studies (such as Computed tomographic colonography (CTC)) and colonoscopy. Each modality differs in terms of test performance characteristics, invasiveness, safety and costs. The objective of this study is to perform an economic evaluation of CRC screening considering all of the available CRC screening modalities using a Canadian perspective. METHODS Using decision analysis, to compare CRC screening by FIT, fecal DNA, CTC and the most widely utilized CRC screening strategies (FOBT and colonoscopy) with no screening in average risk Canadians aged 50 to 74. Outcomes included the number of colonoscopies required, cancers, death from cancer, cost and cost per quality-adjusted life year (QALY) gained. Model inputs were obtained from the literature and a meta-analysis of adenoma prevalence. A lifetime horizon and 5% discounting was used in the analysis. All costs are reported in Canadian dollars and were inflated to 2007. RESULTS In a hypothetical 100,000 patient cohort, we determined that all strategies (FOBT, fecal DNA, CTC, and colonoscopy) were associated with worse clinical outcomes and higher costs than FIT, and thus were “dominated” by FIT. Compared with no screening, FIT was associated with a cost per QALY gained of $3410. This result was robust to plausible changes in known parameters. CONCLUSIONS CRC screening appears cost-effective by conventional standards in comparison to the most common management of average risk Canadians (no screening). Although some uncertainty exists as to the optimal screening strategy, FIT appears to be the optimal strategy if the primary goal is to minimize the cost at which QALYs are purchased.