Objective: To assess the cost-effectiveness of human immunodeficiency virus (HIV) screening strategies of surgeons and dentists., Design: We constructed a model to project costs and HIV transmissions prevented over 15 years for four screening scenarios: 1) one-time voluntary screening, 2) one-time mandatory screening, 3) annual voluntary screening, and 4) annual mandatory screening. One-time screening occurs only in the first year of the program; annual screening occurs once each year. Under mandatory screening, all practitioners are tested and risks of practitioner-to-patient transmission are eliminated for all practitioners testing positive. Voluntary screening assumes 90% of HIV-positive and 50% of HIV-negative practitioners are tested, and risks of transmission in the clinical setting are eliminated for 90% of HIV-positive surgeons and dentists. All costs and benefits are discounted at 5% per annum over 15 years., Results: Using "best-case" scenario assumptions, we find for surgeons that a one-time voluntary screening program would be most cost-effective, at $899,336 for every HIV transmission prevented. For dentists, the one-time voluntary program also is the most cost-effective, at $139,571 per transmission prevented. Annual mandatory programs were least cost-effective for both surgeons and dentists, at $63.3 million and $2.2 million per transmission prevented, respectively., Conclusions: HIV screening of surgeons and dentists ranks among the more expensive medical lifesaving programs, even using liberal assumptions about program effectiveness. Frequency of screening and whether testing is mandatory or voluntary dramatically affect cost per transmission prevented; these features should be considered carefully in designing specific HIV screening programs.