Factor VIIa (FVIIa) is the triggering enzyme of the blood clotting cascade in hemostasis and thrombosis and may play an important role in hypercoagulable states. Indeed, certain epidemiologic studies have found elevated FVII coagulant activity to be an independent risk factor for heart disease. However, FVII circulates as the inert zymogen (FVII), the active enzyme (FVIIa), and possibly other forms as well, obscuring the relationship between any specific form of this enzyme and risk of thrombotic disease. New assay techniques based on soluble mutant tissue factor now permit measurement of FVIIa without interference from the large excess of zymogen FVII in plasma. This in turn has enabled direct examination of the role of plasma FVIIa in disease.