Sexual revictimization (experiencing 2 or more rapes) is prevalent and associated with increased risk for posttraumatic stress disorder (PTSD) and substance use. However, no national epidemiologic studies have established the prevalence or relative odds of a range of types of substance use as a function of sexual victimization history and PTSD status. Using three national female samples, the current study examined associations between sexual revictimization, PTSD, and past-year substance use. Participants were 1763 adolescent girls, 2000 college women, and 3001 household-residing women. Rape history, PTSD, and use of alcohol, marijuana, other illicit drugs, and non-medical prescription drugs were assessed via structured telephone interviews of U.S households and colleges in 2005–2006. Chi-square and logistic regression were used to estimate the prevalence and odds of past-year substance use. Relative to single and non-victims: Revictimized adolescents and household-residing women reported more other illicit and non-medical prescription drug use; revictimized college women reported more other illicit drug use. Past 6-month PTSD was associated with increased odds of drug use for adolescents, non-medical prescription drug use for college women, and all substance use for household-residing women. Revictimization and PTSD were associated with more deviant substance use patterns across samples, which may reflect self-medication with substances. Findings also could be a function of high-risk environment or common underlying mechanisms. Screening and early intervention in pediatric, primary care, and college clinics may prevent subsequent rape, PTSD, and more severe substance use.