D-dimer is a product of cross-linked fibrin degradation by the fibrinolytic system. It has been shown to be highly sensitive and moderately specific for venous thromboembolic disease. Thus, the most common clinical use of D-dimer relates to its negative predictive value for deep vein thrombosis and pulmonary embolism. Diagnosis, however, should not be based solely on this parameter, and an integrated strategy that combines clinical approach (pre-test probability), a non-invasive test (ultrasonography or lung scan) and D-dimer assay is highly recommended. Over the last years a number of studies have demonstrated that D-dimer may also enable the prediction of the complications of atherothrombosis inasmuch as the data available suggest a significant association of D-dimer with the risk of coronary artery disease independent of classic risk factors. Moreover, elevated plasma D-dimer seems to be a marker of a systemic prothrombotic state, and anticoagulation can normalize its levels. However, further studies are needed to assess whether or not this parameters is of clinical value to predict or prevent arterial thrombotic events in the single patient.