Our objective was to review systematically studies of interventions to prevent transmission of sexually transmitted infections (STIs) and human immunodeficiency virus (HIV) in heterosexual men. Of 1157 studies identified through database and hand searching, 27 met our inclusion criteria. Most interventions targeted specific groups of men (eg, those attending STI clinics) rather than general populations. Few were conducted with men alone, and most focused on behavioral and social psychological rather than morbidity outcomes. Of 8 interventions designed to reduce STI incidence (including HIV), 5 were successful, 2 were unsuccessful, and 1 had equivocal results. Of the 5 successful interventions, 1 was carried out in the workplace, 1 in the military, and 3 in STI clinics.They included on-site individual counseling and HIV testing, mass communications regarding risk reduction, and multiple-component motivation and skills education in STI clinics. More high-quality research into the effectiveness of interventions targeting heterosexual men is needed, especially methodologically sound trials to evaluate effects on morbidity.