A case-control comparison within the framework of the prospective, multidisciplinary PLAT Study was performed to assess whether altered baseline fibrinolytic variables were associated with an elevated risk of ischemic thrombotic events in patients with documented coronary, cerebral, and/or peripheral atherosclerotic disease. Fibrinogen, D-dimer, tissue plasminogen activator (t-PA) antigen, and fibrinolytic activity before and after venous stasis (delta = difference between the two values), t-PA inhibitor, and lipid levels in 60 atherosclerotic patients with a thrombotic event during the first year of follow-up were compared with those in 94 atherosclerotic patients without such events, who were matched for age, sex, and diagnosis at enrollment. Events were associated with a higher release of delta t-PA antigen (P = .047), higher D-dimer (P = .024), and higher t-PA inhibitor (P = .001) levels. delta Fibrinolytic activity was correlated inversely with t-PA inhibitor (P < .01) and triglycerides (P < .05). D-Dimer was also correlated with systolic blood pressure (P < .01). Atherosclerotic patients at higher risk of thrombotic ischemic events are characterized by increased fibrin turnover and impaired fibrinolytic activity due to high t-PA inhibitor levels. This hemostatic disequilibrium may participate with conventional risk factors such as elevated triglyceride levels and systolic blood pressure in the multifactorial mechanism of ischemic sequelae in patients with preexisting vascular atherothrombotic disease.