Background: D-dimer is a fibrinogen degradation product formed by the breakdown of cross-linked fibrin in a series of enzyme-mediated steps. Since the D-dimer assay allows for detection of thrombin production and endogenous fibrinolysis, it has been increasingly used in clinics as a screening test to exclude venous thromboembolism and disseminated intravascular coagulation. Additionally, D-dimer has been evaluated for determining the initiation of anticoagulation therapy in patients with selected cardiovascular disease. Summary: This narrative review has evaluated the updated evidence from several recent clinical studies/trials and provides a reappraisal of the utility of D-dimer assay for disease prognosis and clinical management decisions in patients with stable coronary artery disease, acute coronary syndrome, and heart failure. We further discussed several confounding factors that may affect circulating levels of D-dimer, including those observed during the COVID-19 pandemic. Key Messages: Better understanding of the pathophysiologic mechanisms underlying D-dimer formation would improve accuracy and specificity of D-dimer as biomarker for predicting long-term outcome of the severity of coronary artery disease and heart failure.

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