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While research has demonstrated a relationship between family structure, family transitions, and adolescent risky sexual behavior (RSB), most studies suffer from methodological limitations (e.g., a narrow definition of family structure, failure to distinguish between parental divorce and other types of family transitions, utilization of predominantly White samples). The current study examines the influence of having lived with a mother-stepfather, mother-cohabiting partner, mother-relative, or single-mother versus having resided with married, biological parents on African American adolescents’ RSB. Past research has not considered families parented by a mother and biological relative which represent a significant proportion of African American families in the United States. The present study additionally examines the effect of mothers’ number of divorces and number of cohabiting separations for adolescents’ RSB net family structure. We further identify potential mediators through which family structures and family transitions associated with risk impact RSB including variation in quality of parenting (caregivers’ nuturant-involved parenting and hostility) and social learning (adolescents’ sexual attitudes and affiliation with sexually active peers). Hypotheses are assessed using OLS regression models predicting RSB among 550 African adolescents from the Family and Community Health Study (FACHS). Variation in caregivers’ parenting, adolescent’s sexual attitudes, and adolescent’s affiliation with sexually active peers linked family structure and family transitions to adolescent RSB, though these variables do not fully explain the effect of family structure and family transitions. Our findings suggest interventions aimed at reducing RSB in adolescence may be particularly vital during times of family instability and would benefit from including caregivers.