The HIV Prevention Trials Network (HPTN) is a worldwide collaborative clinical trials network that brings together investigators, ethicists, community members, and other partners to develop and test the safety and efficacy of interventions designed to prevent the acquisition and transmission of HIV. The U.S. National Institute of Allergy and Infectious Diseases, the U.S. National Institute of Mental Health, Office of The Director, the U.S. National Institute on Drug Abuse, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, all part of the U.S. National Institutes of Health, co-fund the HPTN. The HPTN has collaborated with more than 85 clinical research sites in 19 countries to evaluate new HIV prevention interventions and strategies in populations with a disproportionate HIV burden. The HPTN research agenda – more than 78 trials ongoing or completed with over 172,000 participants enrolled and evaluated – is focused primarily on discovering new HIV prevention tools and evaluating integrated strategies, including biomedical interventions combined with behavioral risk reduction interventions and structural interventions.