This study investigated the effect of self-reported racial discrimination on endothelial responses to acute laboratory mental stress among post-menopausal women. One-hundred thirteen women (n = 94 self-identified as White and n = 19 self-identified as racial/ethnic minority), 43% with type 2 diabetes, reported lifetime experiences of racial/ethnic discrimination. Repeated assessments of flow-mediated dilation were performed at baseline, immediately after 5 min of mental arithmetic and at 20-min recovery. Both White and racial/ethnic minority women reported lifetime discrimination, with rates significantly higher among minorities. Self-reported lifetime discrimination was associated with attenuated flow-mediated dilation at recovery. Confounding variables, including clinical characteristics, mood, personality traits, other life stressors and general distress, did not better account for the effect of racial discrimination. Neither race/ethnicity nor diabetes status moderated the effect. The perceived stressfulness of the mental arithmetic was not associated with the endothelial response. In conclusion, self-reported lifetime discrimination is associated with attenuated endothelial recovery from acute mental stress. Elucidating the effects of discrimination and the biological mechanisms through which it affects the vasculature may suggest interventions to improve health. Copyright © 2012 John Wiley & Sons, Ltd.