During the tenth biennial examination of the Framingham Study, 1315 participants who were free of cardiovascular disease had fibrinogen levels measured. During the ensuing 12 years, cardiovascular disease developed in 165 men and 147 women. For both sexes, the risk of cardiovascular disease was correlated positively to antecedent fibrinogen values higher than the 1.3 to 7.0 g/L (126 to 696 mg/dL) range. The magnitude of the risk diminished with advancing age in women but not in men. Risk for coronary heart disease also was significantly related to fibrinogen level. Here, the magnitude of risk displayed diminishing impact with age, again only in women. Risk of stroke increased progressively with fibrinogen level in men but not in women. The impact of fibrinogen value, considered as a separate variable, on cardiovascular disease was comparable with the major risk factors, such as blood pressure, hematocrit, adiposity, cigarette smoking, and diabetes. Fibrinogen values were also significantly related to these risk factors. Taking all these into account in a multivariate analysis, fibrinogen level was still significantly related to the incidence of cardiovascular disease in men and marginally significant in women. For coronary heart disease, the fibrinogen level was significant for both men and women. Elevated fibrinogen level is a predictor of cardiovascular disease that should be added to the cardiovascular risk factor profile.