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Introduction and Hypothesis: Intracranial Atherosclerotic Stenosis (ICAS) is associated with 8-10% of all strokes in the U.S. Although there is evidence in the Asian population that inflammation plays a role in ICAS, it has not been shown in the U.S. population. We hypothesized that midlife sensitivity C-reactive protein (hs-CRP), a marker of inflammation, is associated with late-life ICAS in the U.S. population.Methods: The Atherosclerosis Risk in Communities (ARIC) study recruited participants from four U.S. communities between 1987-1989. In the ancillary Dental ARIC study, dentate subjects from ARIC undergoing full-mouth examination also had blood samples obtained to measure the serum inflammatory marker, hs-CRP (1996-1998). High sensitivity ELISA assay that had been validated against nephelometry, was used to measure hs-CRP. Of this cohort, a subset (N=909) underwent high resolution 3T magnetic resonance angiogram at a follow-up visit (2011-2013). All images were analyzed in a centralized lab and ICAS was graded as no stenosis/<50% stenosis, or ≥50% stenosis/complete occlusion. Crude and adjusted Odds Ratio (OR, adjusted for age, gender, race, body mass index, hypertension, diabetes, low density lipoprotein level, and smoking) were calculated to test the association between hs-CRP (stratified as <1, 1-3 and >3 mg/l), and ICAS.Results: A total of 909 subjects (mean age 62±6, 45% male, 81% Caucasian and 19% African-American), underwent assessment of hs-CRP and ICAS. Compared with the reference group (hs-CRP <1 mg/l) modestly elevated hs-CRP (1-3 mg/l) was not significantly associated with >50% ICAS, on univariate (Crude OR 1.3 95% CI: 0.9-2.0) or multivariable analysis (Adjusted OR 1.3, 95% CI: 0.9-2.0). Elevated hs-CRP (>3mg/l) was significantly associated with >50% ICAS in both univariate (Crude OR 1.6, 95% CI:1.1-2.3) and adjusted model (Adjusted OR 1.6, 95% CI:1.1-2.4).Conclusions: In this US population-based community study, we report a significant and independent association between inflammatory marker hs-CRP and ICAS. Further studies are required to test if anti-inflammatory drugs or diet prevents ICAS.