BACKGROUND AND OBJECTIVES: Homeless women have shown high rates of substance use disorders (SUD), but many studies are more than a decade old, limited in geographic location, or focus only on women living outdoors or in shelters. The purpose of this study was to obtain a more current and representative sample of homeless women and the prevalence and predictors of substance use disorders among women seeking primary care at Health Care for the Homeless clinics across the US. METHODS: Eleven Health Care for the Homeless (HCH) clinics in nine states contributed proportionally to a sample of n = 780 female patients who completed a self-administered survey including demographics, housing history, health, mental health, and drug and alcohol use. RESULTS: Compared to the general population of women, rates were four times higher for an alcohol use disorder, and 12 times higher for a drug use disorder. DISCUSSION AND CONCLUSIONS: The findings indicate a significant need for SUD services, with an equally high need for mental health services. In addition, high rates of victimization and use of tobacco, and overall poor health status, indicate overall health disparities. SCIENTIFIC SIGNIFICANCE: Addressing barriers to full integration of substance use and mental health services, such as improving screening, reimbursement, clinician training, and addressing biases about motivation of this population to engage in treatment, are necessary to improve the health of women seeking care in HCH settings. (Am J Addict 2017;26:680-688).