A community-based mail survey of 155 urban American Indian women revealed 91% engaged in at least one lifetime HIV sexual or drug risk behavior, including 19% who had sex with an injection drug user and 7% who had traded sex. Sixty-eight percent of the respondents were sexually active in the last year, with more than half never using condoms. Six percent had ever injected nonprescription drugs; 62% drank alcohol in the last year, with 28% reporting at least one occasion of consuming six or more drinks containing alcohol. Respondents reported high rates of lifetime physical (37%) and sexual (39%) assault, which was generally associated with lifetime but not more recent indicators of sexual and drug risk behavior. Injection drug use mediated the relationship between nonpartner sexual (but not physical) trauma and high-risk sexual behaviors. Findings underscore the need for the integrated assessment and treatment of abuse and substance use as well as more research on the risk behaviors of this understudied and underserved population.