Plasma fibrinogen is a consistent predictor of ischemic heart disease (IHD) in prospective studies, but there are fewer data relating other hemostatic variables to IHD and also to stroke. We therefore studied the relationships of plasma fibrinogen, von Willebrand factor antigen, tissue plasminogen activator (TPA) antigen, factor VII, and fibrin D-dimer to incidence of IHD and stroke and determined whether any associations could be explained by conventional risk factors and baseline heart disease. In the Edinburgh Artery study, 1592 men and women aged 55 to 74 years, randomly sampled from the general population, were followed prospectively over 5 years to detect fatal and nonfatal IHD and stroke events. During the 5 years, 268 new vascular events were identified. Baseline plasma fibrinogen was independently related to risk of stroke in multivariate analysis that adjusted for cigarette smoking, LDL-cholesterol, systolic blood pressure, and preexisting IHD (relative risk [RR] 1.52, 95% confidence interval [CI] 1.17, 1.98). TPA antigen, and fibrin D-dimer were also independently associated with risk of stroke (RR 1.69,95% CI 1.22,2.35 and RR 1.96, 95% CI 1.12,3.41, respectively). Significant relationships were found between TPA antigen and myocardial infarction (P < or = .05). In older men and women, increased coagulation activity and disturbed fibrinolysis are predictors of future vascular events (both IHD and stroke).