The relation of hemostatic factor levels to the occurrence of cardiovascular disease is incompletely established. The Atherosclerosis Risk in Communities Study measured fibrinogen, factor VII, factor VIII, von Willebrand factor, antithrombin III, protein C, activated partial thromboplastin time, and other cardiovascular risk factors in nearly 15,000 men and women aged 45 to 64. This analysis assessed the relations of these hemostatic factors with prevalent cardiovascular disease and asymptomatic carotid artery intimal-medial thickness measured by B-mode ultrasound. Compared with participants without cardiovascular disease, those with cardiovascular disease had higher levels of fibrinogen, factor VIII, and von Willebrand factor in both sexes. The other hemostatic factors were less consistently associated with prevalent cardiovascular disease. Only fibrinogen was associated with carotid intimal-medial thickness. Adjusted for age, race, and field center, the odds ratio for carotid wall thickness in the 90th percentile or greater, compared with < 50th percentile, for each SD higher fibrinogen concentration (65 mg/dL) was 1.42 (95% confidence interval, 1.25, 1.62) in men and 1.43 (1.25, 1.64) in women. This population-based study provides further evidence that fibrinogen and possibly factor VIII and von Willebrand factor are risk factors for cardiovascular disease.