Transgender populations in the United States have been impacted by the HIV/AIDS epidemic. This systematic review estimates the prevalence of HIV infection and risk behaviors of transgender persons. Comprehensive searches of the US-based HIV behavioral prevention literature identified 29 studies focusing on male-to-female (MTF) transgender women; five of these studies also reported data on female-to-male (FTM) transgender men. Using meta-analytic approaches, prevalence rates were estimated by synthesizing weighted means. Meta-analytic findings indicated that 27.7% (95% confidence interval [CI], 24.8-30.6%) of MTFs tested positive for HIV infection (four studies), while 11.8% (95% CI, 10.5-13.2%) of MTFs self-reported being HIV-seropositive (18 studies). Higher HIV infection rates were found among African-American MTFs regardless of assessment method (56.3% test result; 30.8% self-report). Large percentages of MTFs (range, 27-48%) reported engaging in risky behaviors (e.g., unprotected receptive anal intercourse, multiple casual partners, sex work). Prevalence rates of HIV and risk behaviors were low among FTMs. Contextual factors potentially related to increased HIV risk include mental health concerns, physical abuse, social isolation, economic marginalization, and unmet transgender-specific healthcare needs. Additional research is needed to explain the causes of HIV risk behavior of transgender persons. These findings should be considered when developing and adapting prevention interventions for transgender populations.