OBJECTIVE To examine the relationship of adolescent substance use and dependence to sexual risk-taking behavior in late adolescence and young adulthood. METHODS We prospectively examined self-reported sexual behaviors and substance involvement questionnaires in a sample of youth in substance abuse treatment programs and a comparison sample of sociodemographically similar community youths without histories of substance use disorders recruited from media ads. Assessments of sexual behaviors and substance involvement (78% white, 51% female) were collected at 2, 4, and 6 years after initial assessments, as they transitioned from middle adolescence to young adulthood (from age 15.5 to age 21.5 years, on average). The two samples were compared using Chi-square, analysis of variance, and multivariate analysis of variance approaches. Continuous indicators of high-risk sexual behaviors and substance involvement were analyzed with multiple regression. RESULTS Earlier age of onset to sexual activity, more sexual partners, less consistent use of condoms, more sexually transmitted diseases (STDs), and greater prevalence of human immunodeficiency virus testing were reported by youth in the clinical treatment sample relative to sociodemographically comparable nonabusing community youth. High rates of STDs were found among females, and more substance-abusing females reported pregnancies than community females. Substance involvement continued to be associated with high-risk sexual behavior throughout the transition into young adulthood. CONCLUSIONS Youth identified with substance problems are more likely to engage in risky sexual behaviors during adolescence and to continue risky sexual behaviors to the extent that substance problems persist. Risk reduction education should be included with adolescent substance abuse treatment.