Background Previous research has indicated that women and blacks have worse outcomes after acute ischemic stroke (AIS). Little research has been done to investigate the combined influence of race and gender in the presentation, treatment, and outcome of patients with AIS. We sought to determine the association of race and gender on initial stroke severity, thrombolysis, and functional outcome after AIS. Methods AIS patients who presented to 2 academic medical centers in the United States (2004-2011) were identified through prospective registries. In-hospital strokes were excluded. Stroke severity, measured by admission National Institutes of Health Stroke Scale (NIHSS) scores, treatment with tissue plasminogen activator (tPA), neurologic deterioration (defined by a ≥2-point increase in NIHSS score), and functional outcome at discharge, measured by the modified Rankin Scale, were investigated. These outcomes were compared across race/gender groups. A subanalysis was conducted to assess race/gender differences in exclusion criteria for tPA. Results Of the 4925 patients included in this study, 2346 (47.6%) were women and 2310 (46.9%) were black. White women had the highest median NIHSS score on admission (8), whereas white men had the lowest median NIHSS score on admission (6). There were no differences in outcomes between black men and white men. A smaller percentage of black women than white women were treated with tPA (27.6% versus 36.6%, P <.0001), partially because of a greater proportion of white women presenting within 3 hours (51% versus 45.5%, P =.0005). Black women had decreased odds of poor functional outcome relative to white women (odds ratio [OR] =.85, 95% confidence interval [CI].72-1.00), but after adjustment for baseline differences in age, NIHSS, and tPA use, this association was no longer significant (OR = 1.2, 95% CI.92-1.46, P =.22). Black women with an NIHSS score less than 7 on admission were at lower odds of receiving tPA than the other race/gender groups, even after adjusting for arriving within 3 hours and admission glucose (OR =.66, 95% CI.44-.99, P =.0433). Conclusion Race and gender were not significantly associated with short-term outcome, although black women were significantly less likely to be treated with tPA. Black women had more tPA exclusions than any other group. The primary reason for tPA exclusion in this study was not arriving within 3 hours of stroke symptom onset. Given the growth in incident strokes projected in minority groups in the next 4 decades, identifying factors that contribute to black women not arriving to the emergency department in time are of great importance. © 2014 by National Stroke Association.