The purpose of this analysis was to compare substance use disorder (SUD) diagnoses, severity, comorbidity, and course in 362 American Indian veterans. The sample was drawn from communities in the north central and southwestern areas of the United States, structured to over-sample women and to include half-rural/half-urban residents. Instruments used in the study included current demography, military history, the Diagnostic Interview Schedule/Quick Version, Michigan Alcoholism Screening Test modified to include alcohol and drugs (MAST/AD), Brief Symptom Inventory, Posttraumatic Checklist, and a treatment algorithm. Univariate analyses showed that women had lower scores on the MAST/AD, reported lower symptom levels on the Posttraumatic Checklist, and were less apt to use VA mental health services, but were more willing to seek mental health treatment if needed (with probabilities of.01 to.001). At borderline probabilities (.02 to.05), women were younger and had more education, whereas men had more drug-related diagnoses and more combat exposure. On binary logistic regression, women were less apt to have a drug diagnosis and had lower MAST/AD scores; the other differences were not significant. Female American Indian veterans with SUD manifested many of the same gender-related differences as women in the population at large, but with some exceptions (eg, comorbidity). Trauma, PTSD, and continuing posttraumatic symptoms occurred frequently in both male and female veterans of American Indian heritage. VA facilities should out-reach to American Indian women, who report a willingness to seek mental health services but may avoid VA care.