Smoking is a major cause of both chronic obstructive pulmonary disease (COPD) and coronary heart disease, the latter being more common in individuals with COPD. Acute coronary events are usually caused by the development of a platelet-rich thrombus associated with atheromatous plaque rupture or erosion. Levels of systemic biomarkers of inflammation and hemostasis may reflect the presence of atherosclerosis and predisposition to thrombosis, and may allow identification of "vulnerable plaque" and "vulnerable blood" in "vulnerable patients." Hemostasis and inflammation, often viewed as separate processes, are integrated closely, and their response to smoking likely has contributed to the current coronary heart disease epidemic. Coagulation is initiated after exposure of blood to tissue factor present in atheromatous plaques. Fibrinogen and other hemostatic factors important in thrombus formation are influenced by inflammatory stimuli, possibly reflecting both vascular and systemic inflammation. Smokers who develop COPD may have higher basal levels of inflammatory markers, such as fibrinogen, due to lung damage, and respiratory infections to which they are prone may further increase levels, predisposing smokers to coronary events. In summary, smoking predisposes to coronary heart disease and the mechanisms may involve proinflammatory and procoagulant changes. These changes may be more marked in smokers with COPD.