BACKGROUND: Because men transmit Chlamydia trachomatis to women, screening men to prevent pelvic inflammatory disease in women may be a viable strategy. However, the cost-effectiveness of this approach requires careful assessment. METHODS: Data from a demonstration project and longitudinal study that examined screening men for chlamydia were applied to a compartment-based transmission model to estimate the cost-effectiveness of screening men for chlamydia compared with alternative interventions, including expanded screening of women and combining disease investigation specialist-provided partner notification with screening. Cases of pelvic inflammatory disease and quality-adjusted life years lost were the primary outcome measures. A male screening program that screened 1% of men in the population annually was modeled. RESULTS: A program targeting high-risk men for screening (those with a larger number of partners in the previous year than the general population and a higher chlamydia prevalence) was cost saving compared with using equivalent program dollars to expand screening of lower-risk women. Combining partner notification with male screening was more effective than screening men alone. In sensitivity analyses, the male program was not always cost saving but averaged $10,520 per quality-adjusted life year saved over expanded screening of women. CONCLUSIONS: Screening men can be a cost-effective alternative to screening women, but the men screened must have a relatively high prevalence compared with the women to whom screening would be expanded (under baseline assumptions, the prevalence in screened men was 86% higher than that of screened women). These modeling results suggest that programs targeting venues that have access to high-risk men can be effective tools in chlamydia prevention.