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Background: Previous data are conflicting as to whether imbalance between hemostatic factors is associated with clinical strokes. We evaluated the association between hemostatic factor levels and subclinical lacunar infarcts in a nested sample from a subset of the Atherosclerosis Risk in Communities (ARIC) cohort. Methods: 196 cases without clinical strokes had lacunar infarcts by MRI, and 214 controls without radiographic infarcts were frequency-matched by age group and sex. Logistic regression models were fitted to assess the association between levels of hemostatic markers and case status. Results: In age-, race- and sex-adjusted models, von Willebrand factor (vWF) and D-dimer were positively associated with case status, with odds ratios for the highest vs. lowest tertile of 2.0 (95% CI 1.2–3.6) for vWF and 1.76 (95% CI 1.02–3.0) for D-dimer. Plasminogen had nonsignificant inverse associations with presence of silent lacunar infarcts. Conclusions: vWF and D-dimer were positively associated, and plasminogen was nonsignificantly inversely associated with subclinical radiographic infarct. Further studies on the role of these hemostatic factors in the development of silent lacunar infarcts may help elucidate the mechanisms behind this injury and may even point to potential targets for future intervention.