Abstract: With the goal of maintaining mission readiness, the U.S. Department of Defense monitors a variety of health behaviors among its active duty military service members, including sexual health, HIV, and other sexually transmitted infections. Newer biomedical approaches to HIV prevention and care (e.g., Treatment as Prevention (TasP) via Pre-exposure Prophylaxis (PrEP) and undetectable = untransmissible of antiretroviral therapy (ART/U = U) have evolved over the last few years and are now available. However, the last systematic review on HIV prevention among military populations was published in 2005, calling for the need to provide an update on what HIV prevention research has been conducted with U.S. active duty service members. PRISMA guidelines were followed to identify articles that met pre-determined eligibility criteria. Several electronic databases were searched, including PubMed. The review focused on HIV prevention research conducted with the U.S. Military (i.e., active duty service members). Inclusion criteria for articles centered on population (U.S. active duty service members aged 17 years and older), language (published in English), study focus (epidemiological, intervention), study design (descriptive, quasi-experimental, and experimental), date of publication, and research focus. Studies with a descriptive focus to understand HIV-related risk behaviors, use of prevention strategies (e.g., condoms, testing, PrEP), and prescribing practices for uptake of prevention strategies among U.S. military service members (i.e., by providers, uptake from nonproviders) were included. Studies that focused on intervening or changing HIV risk (i.e., interventions) among U.S. military service members were also included. The findings in this review were reported based on the PRISMA guidelines. A total of 2,270 articles were identified through electronic databases. Of the 2,270 articles, 809 articles were removed for duplication. Titles and abstracts were reviewed for the remaining 1,461 articles. Of the 1,461 articles, 1,432 were excluded for not meeting the inclusion criteria. In total, 29 studies met the inclusion criteria and were included in this review. Studies were organized into 3 tables based on study focus and target population (e.g., active duty, U.S. Military service members who were providers vs. nonproviders). The present systematic review describes 29 HIV prevention studies that have been conducted with active duty service members in the U.S. Military since 2000. Overall, most included studies were descriptive, epidemiological studies conducted with active duty service members who were not providers. There were few interventions that reported some success in improving prevention knowledge and condom use. None of the interventions included newer evidence-based strategies of TasP. Although some research had been conducted about PrEP, particularly with providers, there is a clear need for additional studies and interventions to include TasP, given the evidence base of these approaches for reducing acquisition and/or onward transmission of HIV.