Plasma fibrinogen is a major determinant of platelet aggregation and blood viscosity. The decrease in plasma fibrinogen by bezafibrate is associated with a decrease in the risk of reinfarctions. To strengthen the predictive value of plasma fibrinogen with respect to cardiovascular risk, we performed a meta-analysis of studies conducted between 1984 and 1998. Emphasis has been put on the relationship between high levels of plasma fibrinogen and fatal and/or nonfatal cardiovascular events in both the general population and in patients with previous cardiovascular events. Twenty-two studies (13 prospective, 5 cross-sectional, and 4 case-control) addressing the association between fibrinogen plasma concentrations and cardiovascular disease were analyzed. The overall estimate of risk of cardiovascular event in subjects with plasma fibrinogen levels in the higher tertile, was twice as high as that of subjects in the lower one (odds ratio, 1.99; 95% confidence interval, 1.85 to 2.13). High plasma fibrinogen levels were associated with an increased risk of cardiovascular disease in healthy as much as in high-risk individuals. A metaregression showed no confounding effects attributable to selected characteristics of retrieved studies. A subgroup analysis (study design, follow up, mean fibrinogen levels, percentage of smokers, and mean age) allowed us to conclude that fibrinogen is an independent risk factor for cardiovascular disease; that it interacts with major determinants of myocardial and cerebrovascular ischemia; and that, in secondary prevention studies, it enhances by 8% the prediction of future events by established risk factors. Thus, fibrinogen measurements should be encouraged to refine the overall risk profiles of individuals and to better tailor preventive interventions.