Background: The U.S. transgender population are a high-risk group for HIV infection. This systematic review estimates the prevalence of HIV infection and risk behaviors of transgender persons living in the U.S. Methods: MEDLINE, EMBASE, PsycINFO, CINAHL, Sociological Abstracts were searched 2006 through February 2016 and CDC’s HIV Prevention Research Synthesis database through August 2016. Eligible reports were U.S.-based studies that included transgender persons (TG) and reported HIV status. Data were double-coded and will be quality assessed. Random-effects models were used to calculate overall prevalence of HIV infection and risk behaviors, for male-to-female (MTF), female-to-male (FTM) and race subgroups. Results: Eighteen studies reported HIV infection from test results and thirty-seven studies were self-reported. Overall prevalence of tested HIV infection was 8.8%(95%CI:5.5%-13.8%)[n=18]. Among MTFs and FTMs, HIV infection was 11.9%(6.9%-19.7%)[n=10] and 2.7%(1.3%-5.6%)[n=6], respectively. Self-reported HIV infection was 16.7%(12.0%-22.7%)[n=37], 20.3%(15.5%-26.0%)[n=25], and 3.1%(0.8%-11.8%)[n=5] for overall, MTF, and FTM subgroups. HIV infection was highest among African Americans, 36.5%(22.9%-52.7%)[n=4]. Any STD diagnosis prevalence was 17.1%(13.4%-21.7%)[n=27] overall and comparable for the MTF and FTM subgroups. Unprotected anal/vaginal intercourse prevalence was also similar between subgroups with an overall prevalence of 37.4%(29.8%-45.7%)[n=28]. Sharing needles for drug use, hormone, or silicone injection was 2.4%(1.0%-5.9%)[n=7]. Conclusions: HIV infection is high for transgender persons in the U.S., particularly for MTF and African American TG. Sampling methods used in most studies limits generalizability to the entire TG population and substantial heterogeneity was observed in analyses. This study provides current estimates to HIV prevention research related to TG persons.