Objective: Recent work has emphasized the role of violent victimization, along with risky contexts like sex exchange, in pathways to problems of externalizing and substance use in women. Nonetheless, few studies have empirically tested gender differences involving the roles of adversity factors (e.g., childhood violent maltreatment, sex exchange) in drug use patterns. The present study tested a model of gender differences in relationships between childhood physical and sexual abuse, sex exchange, and 2 indicators of drug use: engagement and symptoms of disorder. Method: We recruited an ethnically diverse sample of 304 (130 women) adults with recent histories of violence and/or drug use, who completed a substance use diagnostic interview, the Childhood Trauma Questionnaire, and a sex exchange questionnaire. Results: First, structural equation modeling revealed that childhood sexual and physical abuse were related to increased drug engagement in women and men, respectively, above the influence of early childhood contextual variables (e.g., neighborhood, family) and age. Second, sexual abuse was related to sex exchange, which in turn was related to drug use symptoms in women but not men. Conclusions: These data provide empirical support for distinct trauma-related pathways to drug use problems in men and women, which has implications for gendered explanations and prevention approaches. (PsycINFO Database Record (c) 2016 APA, all rights reserved)