African Americans experience a disproportionate mortality, morbidity, and disability associated with ischemic stroke. Traditional risk factors offer some explanation for this finding, but novel risk factors have not been explored. APOE4 genotype, which is more prevalent in African Americans demonstrate a pro-inflammatory phenotype that may result in an exaggerated inflammatory response associated with ischemic stroke, resulting in worse outcomes. The purpose of this study was to examine relationships among APOE genotypes, inflammatory markers (CD11β, platelet leukocyte aggregates, IL-1β, IL-6, IL-8, and tissue necrosis factor alpha), the anti-inflammatory marker, IL-10, and risk factors (hypertension, diabetes type II, obesity, hyperlipidemia, and smoking) in African Americans at 3 days post stroke. Twenty five patients were enrolled with 12 patients in the APOE4 group and 13 patients in the non-APOE4 group. In the APOE4 group, 75% were male compared to 54% in the non-APOE4 group. The average age in the APOE4 group was 56.5 ± 9.0 compared to 66 ± 16.0 years in the non-APOE4 group. Females in the APOE4 group were younger with ages comparable to men. All participants had hypertension. Forty two percent of patients in the APOE4 group had two risk factors and 46% of patients in the non-APOE4 group had three risk factors. Major findings included 1) there were no statistical difference between inflammatory markers and APOE genotypes, and 2) the APOE4 carrier was not a predictor for overall inflammatory load among African Americans with ischemic stroke. The study was underpowered and small effect sizes were not sufficient to create statistical findings. This was the first study to examined APOE genotypes, inflammatory markers, and risk factors among African Americans with ischemic stroke. More studies are needed to not only investigate novel risk factors, but to also characterize inflammatory and genetic mechanisms with ischemic stroke and their associated outcomes among African Americans. Such studies may lead to primary and secondary prevention of ischemic stroke and reduce the health disparities associated with ischemic stroke among African Americans.