OBJECTIVE To examine the effects of prenatal cocaine exposure and biological sex on adolescent risk-taking while controlling for early environmental risk. METHODS Adolescents (n=114, mean age=16) were grouped according to high and low risk-taking propensity as measured by the Balloon Analogue Risk Task (BART). Prenatal cocaine exposure was assessed at birth, while environmental risk was assessed at three points during early childhood. RESULTS A binary regression analysis indicated that males were 3.5 times more likely than females to be high risk-takers. Biological sex and prenatal cocaine exposure interacted such that exposed males were most likely to be high risk-takers while exposed females were the least likely to be high risk-takers. This pattern held after controlling for prenatal alcohol exposure and early environmental risk. Early environmental risk did not predict adolescent risk-taking. CONCLUSIONS These findings complement and extend earlier research demonstrating that prenatal cocaine exposure interacts with biological sex in domains related to inhibitory control, emotion regulation, antisocial behavior, and health risk behaviors during preadolescence.