Transgender women continue to face a significant burden of health disparities with HIV infection as a critical public health concern. Substance use is higher among transgender women compared to cisgender women. However, little is known about transgender women who inject drugs and risk for HIV in the United States. The objectives were to explore HIV prevalence, injection-related behaviors, and HIV prevention and care outcomes among transgender women who inject drugs and to compare transgender women to a general sample of people who inject drugs (PWID). Participants from National HIV Behavioral Surveillance were recruited via respondent-driven sampling, interviewed, and tested for HIV infection in 2019-2020. Log-linked Poisson regression models were used to test for associations between injection drug use and selected characteristics. Among 1,561 transgender women, 7% injected drugs in the past 12 months. HIV prevalence was higher among transgender women who inject (aPR=1.5, 95%CI=1.2-1.8) than those who do not. Multiple psychosocial conditions were associated with injection drug use. Among transgender women with HIV, those who inject were less likely to take antiretroviral therapy (aPR=0.8, 95%CI=0.7-1.0) than those who do not. Methamphetamine was the most commonly injected drug (67%); most accessed a syringe services program (66%). Transgender women who inject have substantial challenges related to health outcomes including high HIV prevalence and exposure to psychosocial conditions, such as homelessness, incarceration, and exchange sex, that may exacerbate risks associated with injection drug use. This population may benefit from increased access to non-judgmental and culturally competent harm reduction services.