OBJECTIVES: This study is an economic evaluation of currently recommended colorectal cancer (CRC) screening procedures, and strategies that incorporate chemopreventive options such as aspirin or a cycooxygenase-2 inhibitor. METHODS: A decision analysis model was constructed to compare alternative CRC screening strategies. A Markov model was employed to simulate the natural history of CRC. Markov states included Well, Well with Polyp History, Well with CRC History, CRC-Local, CRC-Regional, CRC-Distant, and Dead. Quality adjusted life years were used as the primary outcome measure. The base case analysis represents the overall cost and effectiveness associated with each screening strategy. Incremental cost-effectiveness ratios (ICERs) were calculated for each screening strategy. One-way sensitivity analyses were performed to assess the factors that have the greatest effect on the cost-effectiveness of screening. RESULTS: The most cost-effective screening strategy was Fecal Occult Blood Test (FOBT); followed by FOBT plus aspirin, colonoscopy, and colonoscopy plus aspirin. The ICER of FOBT was $13,014.85 compared to natural history or no intervention. The model was sensitive to the costs of FOBT, colonoscopy, and aspirin. The screening strategies were sensitive to the cost of aspirin, FOBT, and colonoscopy. CONCLUSION: Results from the analysis showed that the most cost-effective screening strategy was the use of FOBT yearly. In terms of only cost, FOBT was the least expensive screening strategy whereas the most expensive was colonoscopy plus COX-2 inhibitor. The results from the study suggest that FOBT and colonoscopy, as well as these strategies plus aspirin, are the more cost-effective of all the screening strategies employed. FOBT plus aspirin and colonoscopy have similar cost-effectiveness with colonoscopy having an ICER of only $35.43.