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Introduction: Diabetes mellitus (DM) carries a greater stroke risk for females than males, possibly because of a difference in cardiovascular risk profiles between females and males with DM. Our aim was to compare the sex-specific risk factor profiles for patients with DM with those without DM among patients with acute ischemic stroke (AIS) in the Greater Cincinnati/ Northern Kentucky Stroke Study (GCNKSS).Methods: The GCNKSS ascertained cases of AIS in 2005 and 2010 among adult (age ≥20 years) residents of a biracial population of 1.3 million. Past and current stroke risk factors, obtained via chart review, were compared between those with and without DM using chi-square to examine bivariate differences and multiple logistic regression to examine sex-specific profiles. P < 0.05 was considered statistically significant.Results: There were 3515 patients with incident AIS; 1919 (55%) were female, 697 (20%) were black, and 1146 (33%) had DM. A lower proportion of females with DM were over 65 years old compared with those without DM. The proportion of males >65 with DM was not significantly different from that of males without DM. Among both females and males with DM, significantly more were Black, obese, and had histories of hypertension, high cholesterol, CAD and myocardial infarction compared to those without DM. In sex-specific adjusted analyses, women with DM were significantly less likely to be over 65 and more likely to have CAD than women without DM, whereas age and CAD were not significant factors in differentiating the profiles of men with and without DM.Conclusions: The result that females had their strokes at a younger age if they had a history of DM, and that no such age difference existed in males, suggests that DM is more severe and has a greater negative impact on females than males. As opposed to males, females with DM were also more likely to have CAD compared to those without DM, consistent with a possible sex difference in the association between DM and vascular disease.