Women experience alarming levels of physical and sexual assault, which may lead to escalation of substance use. Reciprocally, evidence from cross-sectional studies indicates that substance use may increase risk of assault. To date, directionality of this relationship remains unclear. This issue is addressed by the present 3-wave longitudinal study in which a national probability sample of 3,006 women were followed for 2 years. Dependent measures were obtained at each wave of the study and included questions about lifetime and new assault status, alcohol abuse, and drug use. Wave 1 use of drugs, but not abuse of alcohol, increased odds of new assault in the subsequent 2 years. Reciprocally, after a new assault, odds of both alcohol abuse and drug use were significantly increased, even among women with no previous use or assault history. For illicit drug use, findings support a vicious cycle relationship in which substance use increases risk of future assault and assault increases risk of subsequent substance use.