To compare and analyze the cost-effectiveness of different mammographic screening strategies.A computer simulation model was developed to compare mammographic screening with observation without screening. Cost-effectiveness was expressed as marginal cost per year of life saved (MCYLS) and was calculated for the following mammographic screening strategies: (1) annual for ages 40 to 79 years; (2) annual for ages 50 to 79 years; (3) biennial for ages 50 to 79 years; (4) annual for ages 40 to 49 years with biennial for ages 50 to 79 years; (5) annual for ages 40 to 64 years with biennial for ages 65 to 79 years; (6) biennial for ages 40 to 49 years with annual for ages 50 to 79 years; and (7) annual for high-risk and biennial for normal-risk women aged 40 to 49 years with annual for ages 50 to 79 years.The probability and cost of all outcomes were established from previously published data or community experience.The most cost-effective screening strategy is biennial mammography for women aged 50 to 79 years, with an MCYLS of $16,000. Adding annual mammography for women aged 40 to 49 years increases the MCYLS to $20,200, but is more cost-effective than other tested protocols that included women in their 40s; annual mammography for ages 40 to 49 years with biennial for ages 50 to 79 years is also more cost-effective than annual mammography for ages 50 to 79 years.Screening programs that include women in their 40s can be as cost-effective as some that exclude such women. Choice of a screening strategy depends on financial resources and desired effectiveness.