Objective: Posttraumatic stress disorder (PTSD) and substance use disorders are a significant comorbid concern among sexual assault survivors. Thus, underlying risk and protective factors are critical to investigate in understanding how to prevent this comorbidity. Method: The current study assessed potential moderating effects of coping self-efficacy (CSE) and emotion dysregulation on the association between sexual assault-related PTSD symptom severity and drug use severity in a sample of college women. In this study, 518 female undergraduate students completed self-report measures of nonconsensual sexual experiences, PTSD symptoms, CSE, emotion dysregulation, and drug use severity. Results: Of these participants, 287 women reported at least 1 incident of attempted or completed rape. We found evidence of a significant moderation effect, suggesting that high levels of CSE and low levels of emotion dysregulation reduce the likelihood of drug use issues for female sexual assault survivors. Conclusions: These findings suggest that assessment tools, interventions, and trauma-related policies should target CSE and emotion dysregulation in attenuating the risk of drug use for women with assault-related PTSD symptoms. Clinical Impact StatementCollege women are at high risk for sexual violence, a public health crisis which is strongly associated with numerous adverse health outcomes. This study is the first evaluation of the conditional effect of PTSD symptom severity on drug use severity contingent upon the influence of both coping self-efficacy and emotion regulation among a sample of women with a history of rape experiences. These findings provide clear clinical implications for informed assessment and intervention practices for mental health providers, including more comprehensive and tailored interventions to reduce the likelihood of drug use issues for women.