The exact mechanisms for thrombus formation in patients with valvular heart disease have not been clearly defined. Abnormalities in plasma coagulation factors indicative of a prothrombotic state may in part account for the risk of stroke and thromboembolism in such patients. The aim of this study was, therefore, to determine the effects of mitral regurgitation (MR) and aortic stenosis (AS) on plasma fibrinogen or fibrin D-dimer levels as indices of a thrombogenic (or prothrombotic) state. A total of 25 patients with valve disease in sinus rhythm were studied: 12 patients (all women; mean age fifty-five years, sem 3.3) with MR; and 13 patients (7 men, 6 women; mean age fifty-seven years, sem 3.5) with AS were studied. Patients with MR had a median plasma fibrinogen that was significantly elevated when compared with female population values (median difference 0.62 g/L; 95% confidence intervals (CI) 0.27 to 1.05, P = 0.0016). However, these patients had a median plasma fibrin D-dimer that was lower than that for population controls (median difference 21 ng/mL; 95% CI 0 to 38, P = 0.05). Patients with aortic valve disease had a median plasma fibrinogen that was significantly increased when compared with population controls (median difference 0.82 g/L; 95% CI 0.34 to 1.24, P = 0.001). These patients had a plasma fibrin D-dimer level that was similar to population values (median difference 3 ng/mL; 95% CI -25 to 22, P = 0.80). Patients with MR or AS have higher plasma fibrinogen levels when compared with "normal" population values, suggesting possible hemorheologic abnormalities in these patients. Subjects with MR had lower plasma fibrin D-dimer levels, suggesting lesser intravascular clotting, consistent with clinical echocardiographic studies. Subjects with AS had plasma fibrin D-dimer levels similar to the "normal" population values, suggestive of a different pathophysiological mechanism for thromboembolism. These findings add to an improved understanding of the relationship between clinical observations and the significance of plasma fibrinogen and fibrin D-dimer levels in thrombogenesis.