Objective: The concurrence of prenatal alcohol exposure with other drug exposure, low socioeconomic status and environmental risk factors may obscure associations, if any, between prenatal cocaine exposure and child outcomes. This study evaluates the effects of prenatal cocaine exposure on child behavior in analyses stratified by gender and prenatal alcohol exposure status. Methods: Maternal alcohol, cigarette, and illicit drug use were prospectively assessed by interview during pregnancy and postnatally. Maternal and neonatal urine were tested for drug exposure as clinically indicated. Caregiver report of child behavior was assessed with the Achenbach Child Behavior Checklist (CBCL). Dichotomous cocaine exposure was characterized as no (negative history and biologic markers), and any (positive history and/or biologic markers during pregnancy and/or positive urine screen at delivery from either mother or infant). Results: Prenatal cocaine exposure was associated with adverse effects on offspring behavior that were moderated by the gender of the offspring as well as prenatal alcohol exposure. For girls without prenatal alcohol exposure, 6.5% of the unique variance in behavior was related to prenatal cocaine exposure. For these girls, the odds of scoring in the abnormal range for Aggression was 17 times control levels (95% confidence limits 1.4 to 203). These findings, though significant, have wide confidence intervals and need to be replicated in larger cohorts and on longitudinal follow-up.