To clarify the best cost-effective screening strategy for colorectal cancer in Japan, the cost-effectiveness ratio was compared among six currently performed procedures. The analysis was made using a simulation model to estimate long-term cost and effectiveness of the screening programs. In the screening by the immunological fecal occult blood test (FOBT), a comparison between the one- and two-day fecal collection methods indicated that the latter was more cost-effective than the former. A comparison was also made on the four workup methods: barium enema (BE) alone, a combination of BE and sigmoidoscopy (BE + SIG), total colonoscopy (TCF) alone, and a combination of BE and TCF (BE + TCF). The cost-effectiveness ratio was the lowest in the method using TCF alone, followed by those based on BE alone and BE + TCF, and the highest in the BE + SIG method. The superiority of TCF alone strategy was stable over a range of estimates such as the sensitivity of diagnostic tests, the probability of complications due to TCF, etc. It is concluded that a combination of the two-day FOBT and TCF yields the best cost-effectiveness.