BACKGROUND To assess the impact of prenatal cocaine exposure (PCE) on adolescent sexual risk behaviors. Externalizing behavior, teen substance use, and early sexual intercourse were examined as pathways mediating the effects of PCE on sexual risk behaviors. METHODS Adolescents (N=364; 185 PCE, 179 non-cocaine exposure (NCE); 205 girls, 159 boys), primarily African-American and of low socioeconomic status, were prospectively enrolled in a longitudinal study at birth. Risky sexual behaviors were assessed at ages 15 and 17. Externalizing behavior at 12 years was assessed with the Youth Self-Report. Substance use, via self-report and biologic assays, and early (before age 15) sexual intercourse were assessed at age 15. Path analyses with the weighted least squares estimator with mean and variance adjustments were performed. RESULTS The final structural equation model-based path model, χ(2)=31.97 (df=27), p=.23, CFI=.99, TLI=.99, RMSEA=.021, WRMR=.695, indicated a direct effect of PCE on sexual risk behavior (β=.16, p=.02). Although PCE was related to greater externalizing behavior (β=.14, p=.009), which in turn, predicted early sexual intercourse (β=.16, p=.03), leading to sexual risk behavior (β=.44, p<.001), bootstrapping indicated a non-significant indirect effect (β=.01, p>.10). Substance use was correlated with early sexual intercourse (r=.60, p<.001) and predicted sexual risk behavior by age 17 (β=.31, p=.01). CONCLUSIONS Prenatal cocaine exposure was related to more engagement in sexual risk behaviors, suggesting the importance of reducing substance use among pregnant women as a means of prevention of offspring substance use and sexual risk behavior.