Transgender youths (those whose gender identity* does not align with their sex†) experience disparities in violence victimization, substance use, suicide risk, and sexual risk compared with their cisgender peers (those whose gender identity does align with their sex) (1-3). Yet few large-scale assessments of these disparities among high school students exist. The Youth Risk Behavior Survey (YRBS) is conducted biennially among local, state, and nationally representative samples of U.S. high school students in grades 9-12. In 2017, 10 states (Colorado, Delaware, Hawaii, Maine, Maryland, Massachusetts, Michigan, Rhode Island, Vermont, Wisconsin) and nine large urban school districts (Boston, Broward County, Cleveland, Detroit, District of Columbia, Los Angeles, New York City, San Diego, San Francisco) piloted a measure of transgender identity. Using pooled data from these 19 sites, the prevalence of transgender identity was assessed, and relationships between transgender identity and violence victimization, substance use, suicide risk, and sexual risk behaviors were evaluated using logistic regression. Compared with cisgender males and cisgender females, transgender students were more likely to report violence victimization, substance use, and suicide risk, and, although more likely to report some sexual risk behaviors, were also more likely to be tested for human immunodeficiency virus (HIV) infection. These findings indicate a need for intervention efforts to improve health outcomes among transgender youths.