Cigarette smoking has long been associated with thrombotic vascular disease. Smoking is associated with a two- to fourfold increase in risk of coronary heart disease and a greater than 70% excess rate of death from coronary heart disease. Smoking acts in synergy with other factors (hypertension, hypercholesterolemia, diabetes) to further increase the risk of coronary disease. 1 , 2 Smokers account for 70% of patients with atherosclerosis obliterans and virtually all those with thromboangiitis obliterans. 1 There is a higher risk of stroke and stroke-related mortality in smokers compared to nonsmokers, especially in younger individuals. 1 , 3 Since many of these diseases are associated with abnormalities of the fibrinolytic system, it is not unexpected that many investigators have postulated that chronic cigarette smoking might impair fibrinolysis. This chapter summarizes the abnormalities found in the fibrinolytic system of chronic smokers and, in an attempt to determine how these abnormalities arise, reviews the conflicting data on the effect of acute cigarette smoking on fibrinolysis.