Acquired qualitative abnormalities of fibrinogen molecules, termed acquired dysfibrinogenemia, have been demonstrated in several disease states mostly related to prothrombotic tendency, including multiple myeloma and liver disease. Fibrin is abundant in atherosclerotic plaques. Altered plasma fibrin properties, reflected usually by reduced clot permeability and impaired fibrinolysis, have been reported in patients with acute or prior myocardial infarction, ischemic stroke, and peripheral artery disease. Moreover, prothrombotic clot phenotype has been observed in patients with previous no-reflow phenomenon and stent thrombosis. Growing evidence indicates that acquired dysfibrinogenemia contributes to the progression of atherosclerotic vascular disease and the occurrence of its thrombotic manifestations. The review summarizes current knowledge on the links between fibrin clot phenotype and atherosclerotic vascular disease and describes a wide spectrum of cardiovascular risk factors as modifiers of fibrin network characteristics.