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OBJECTIVE:: High-risk environments characterized by familial substance use, poverty, inadequate parental monitoring, and violence exposure are associated with an increased propensity for adolescents to engage in risk-taking behaviors (e.g., substance use, sexual behavior, and delinquency). However, additional factors such as drug exposure in utero and deficits in inhibitory control among drug-exposed youth may further influence the likelihood that adolescents in high-risk environments will engage in risk-taking behavior. This study examined the influence of prenatal substance exposure, inhibitory control, and sociodemographic/environmental risk factors on risk-taking behaviors in a large cohort of adolescents with and without prenatal cocaine exposure (PCE). METHOD:: Risk-taking behavior (delinquency, substance use, and sexual activity) was assessed in 963 adolescents (433 cocaine-exposed, 530 nonexposed) at 15 years of age. RESULTS:: Prenatal cocaine exposure predicted later arrests and early onset of sexual behavior in controlled analyses. Associations were partially mediated, however, by adolescent inhibitory control problems. PCE was not associated with substance use at this age. In addition, male gender, low parental involvement, and violence exposure were associated with greater odds of engaging in risk-taking behavior across the observed domains. CONCLUSIONS:: Study findings substantiate concern regarding the association between prenatal substance exposure and related risk factors and the long-term outcomes of exposed youth. Access to the appropriate social, educational, and medical services is essential in preventing and intervening with risk-taking behaviors and the potential consequences (e.g., adverse health outcomes and incarceration), especially among high-risk adolescent youth and their families