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Introduction: Overall ischemic stroke (IS) incidence has declined in the US, but has remained stable among midlife (age 45-59) adults and is higher in midlife Mexican Americans (MAs). We examined the contribution of stroke risk factors to ethnic differences in IS rates among midlife MAs and non-Hispanic Whites (NHWs) in a population-based study.Methods: Incident IS (N=823) counts and corresponding risk factors were identified from the BASIC Project, Nueces County, Texas (2000-2010). US Census data (2000) for Nueces County was used to estimate the population at-risk for stroke, and the Texas Behavioral Risk Factor Surveillance System for Public Health Region 11(2000-2010) was used to estimate prevalence of risk factors in the stroke free population. Poisson regressions were run combining stroke counts (numerator) and population at-risk counts (denominator) classified by ethnicity and risk factor status to estimate unadjusted and risk factor adjusted associations between ethnicity and IS rates. Separate models were run for each risk factor (diabetes, hypertension, coronary heart disease, high cholesterol, education < high school, no health insurance, current smoking, BMI>30), and extended to include an interaction term between ethnicity and risk factor.Results: The crude ethnic IS rate ratio (RR) comparing MAs with NHWs was 2.13 (95% CI: 1.84-2.47). The ethnic RR was lower in models that adjusted for diabetes (RR:1.54; 95% CI: 1.31-1.78), hypertension (RR: 1.92; 95% CI: 1.65-2.22), and education < high school (RR: 2.02; 95% CI: 1.72-2.38) compared to the crude association. Ethnicity significantly modified associations between diabetes, smoking, health insurance, education and IS rates. Associations between diabetes and IS rates was greater among MAs (RR: 6.82, 95% CI: 5.76-8.07) compared with NHWs (RR: 4.40, 95% CI: 3.33-5.81), while smoking associations were greater in NHWs (MA RR: 2.61, 95% CI: 2.20-3.10; NHW RR: 3.49, 95% CI: 2.73-4.46). Socioeconomic variables increased IS risk in NHWs but were insignificant or protective in MAs.Conclusion: Traditional stroke risk factors may contribute to midlife ethnic stroke disparities; particularly diabetes, given its high prevalence and stronger association with IS among midlife MAs as compared with NHWs.