Abstract-The coagulation and fibrinolytic systems safeguard the patency of the vasculature and surrounding tissue. Cross regulation of coagulation and fibrinolysis plays an important role in preserving a balanced hemostatic process. Identification of Thrombin Activatable Fibrinolysis Inhibitor (TAFI) as an inhibitor of fibrinolysis and one of the main intermediates between coagulation and fibrinolysis, greatly improved our understanding of cross regulation of coagulation and fibrinolysis. As TAFI is an enzyme that is activated by thrombin generated by the coagulation system, its activation is sensitive to the dynamics of the coagulation system. Defects in coagulation, such as in thrombosis or hemophilia, resonate in TAFI-mediated regulation of fibrinolysis and imply that clinical symptoms of coagulation defects are amplified by unbalanced fibrinolysis. Thrombomodulin promotes the generation of both antithrombotic activated protein C (APC) and prothrombotic (antifibrinolytic) activated TAFI, illustrating the paradoxical effects of thrombomodulin on the regulation of coagulation and fibrinolysis. This review will discuss the role of TAFI in the regulation of fibrinolysis and detail its regulation of activation and its potential therapeutic applications in thrombotic disease and bleeding disorders. Key Words: coagulation Ⅲ fibrinolysis Ⅲ carboxypeptidase B Ⅲ TAFI Ⅲ thrombomodulin Ⅲ APC Ⅲ hemophilia T hrombin Activatable Fibrinolysis Inhibitor (TAFI) is an enzyme that is activated by thrombin generated by the coagulation system and which downregulates fibrinolysis. It is, therefore, considered to play an important role in the regulation of fibrinolysis by the coagulation system. Independent identification of TAFI by different groups resulted in different nomenclature for the same protein. Consequently, activated TAFI (TAFIa), plasma carboxypeptidase B (pCPB), carboxypeptidase U (CPU), or carboxypeptidase R (CPR) are all used in literature to denote the active enzyme TAFIa, whereas TAFI, procarboxypeptidase U (pro-CPU), plasma procarboxypeptidase B (pro-pCPB), or procarboxypeptidase R (pro-CPR) are used to denotes the zymogen, TAFI. [1][2][3][4] In this review TAFI will be used to indicate the zymogen and TAFIa to indicate the enzyme.Activation of TAFI by thrombin is greatly enhanced in the presence of thrombomodulin and this presents two distinct pathways for TAFI activation: (1) by relative low concentrations of thrombin in the presence of thrombomodulin, and (2) by relative high concentrations of thrombin generated via the intrinsic pathway of coagulation in the absence of thrombomodulin. Activation of TAFI is therefore sensitive to the dynamics of coagulation and so is its inhibition of fibrinolysis. The fact that TAFIa inhibits fibrinolysis by modulating the fibrin cofactor function for plasmin generation, rather than by direct irreversible inhibition, and the fact that the activity of TAFIa is short-lived contribute to the dynamics of this system.The discovery of TAFI greatly facilitated our understanding of cr...