Substance use and sexual risk behaviors continue to be major concerns for today's youths, and are particularly problematic for those who have been placed in out-of-home care settings. The purpose of this study was to explore these associations in a sample of 120 girls placed in a residential treatment setting and attending an on-site school in a major metropolitan area in the Midwest. A modified Youth Risk Behavior Survey (YRBS) was administered including questions relating to the youths' foster care or adjudicated status. The substance use variables targeted were alcohol and drug use. The sexual risk behavior variables were age of onset of first sexual intercourse, virginity status, contraceptive use, age of first sexual partner, and experience with ever having been forced to have sex. Results indicate that earlier onset and greater frequency of substance use were both correlated with number of sexual partners. Frequency of substance use was a significant and consistent contributor. Age of sexual partner was an inconsistent contributor, and history of forced sexual activity was not a contributor. Implications for policy and practice are offered to enhance the health and well-being of this unique population.