This study examined the HIV risk behaviors and life experiences of 151 transgender female youth, ages 15-24, in Los Angeles and Chicago. Descriptive analyses and logistic regression modeling were used to identify life factors associated with ever having engaged in sex work. Sixty-seven percent of participants had ever engaged in sex work and 19% self-reported being HIV positive. Many factors were significantly associated with sex work for this sample population. A final multivariate logistic regression model found that lower education status, homelessness, use of street drugs, and perceived social support remained significantly associated with sex work when controlling for other factors. Findings highlight the complex HIV risk environment and suggest a need for sex work initiation research for transgender female youth. HIV prevention efforts for this population need to include broad-based approaches that take into account individual, social, and community-level factors relevant to the lives of transgender female youth.