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Background: African Americans with hypertension have higher cardiovascular morbidity and mortality than hypertensives from other ethnic groups. Plasma D-dimer, a fragment generated from fibrin during lysis of mature clot in vivo, is a predictor of adverse cardiovascular events. Objective: We investigated whether plasma levels of D-dimer differ between African American (AA) and non-Hispanic white (NHW) adults with hypertension. Methods: Participants included 933 AA (65 ± 9 years, 72% women) and 821 NHW (61 ± 9 years, 56% women) from the community. D-dimer was measured using an immunoturbidimetric assay. Multivariable regression analyses, stratified by gender, were performed to assess whether AA ethnicity was associated with D-dimer levels after adjustment for age, body mass index (BMI), total and high-density lipoprotein (HDL) cholesterol, systolic blood pressure, diabetes, history of smoking, medication (statin and aspirin) use, lifestyle variables (physical activity, alcohol intake, and education), estimated glomerular filtration rate (eGFR), and a marker of inflammation, C-reactive protein (CRP). Results: D-dimer levels were higher in AA men and women than in their NHW counterparts (mean ± SD; men 256 ± 199 vs. 190 ± 183 ng mL−1, P<0.001; women, 290 ± 233 vs. 225 ± 195 ng mL−1, P<0.001). In both sexes, after adjustment for age, conventional risk factors, medication use, and lifestyle variables, AA ethnicity remained associated with higher D-dimer levels (P=0.002 in men, P=0.006 in women). These associations remained significant after additional adjustment for eGFR and plasma CRP (P=0.003 in men, P<0.0001 in women). Conclusions: Among adults with hypertension, AA ethnicity was independently associated with higher plasma levels of D-dimer.