Objective: To investigate the direct effects of prenatal cocaine exposure (PCE) on adolescent drug use, while controlling for other predictors of adolescent use. Method: Data are from a longitudinal study of PCE in which women and their offspring were assessed throughout childhood. Adolescents were interviewed at 15 years about their age at initiation of alcohol, marijuana, and tobacco. The sample consisted of 214 adolescents and their caregivers: 50% was of white ethnicity, and 50% African American. Results: First trimester cocaine exposure significantly predicted earlier adolescent marijuana and alcohol initiation. The hazard of marijuana and alcohol initiation among exposed adolescents was almost two times greater than among nonexposed adolescents, adjusting for other significant factors. There were no differences in tobacco initiation. Other significant predictors of adolescent drug use were family history of alcohol problems, exposure to violence, and childhood maltreatment. Conclusions: Cocaine exposure during early pregnancy was associated with initiation of marijuana and alcohol use. Exposure to violence, childhood maltreatment, and familial factors also predicted adolescent initiation, but did not mitigate the effects of PCE. The combination of these risk factors has significant implications for the development of later substance use, social, and psychiatric problems. (Contains 3 figures and 3 tables.)