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To investigate thrombin activatable fibrinolysis inhibitor (TAFI) in ischemic stroke and its relationship to fibrinolysis and inflammation, we investigated 32 patients with ischemic stroke during the acute phase and after 60 days. TAFI antigen levels, global markers of hemostasis (coagulation and fibrinolysis) and inflammatory markers were measured in plasma. TAFI antigen levels were significantly elevated at admission (128%; 109–151%) and at day 1 (129%; 109–152%) compared with day 60 (108%; 91–127%; both P < 0.01) and with healthy control individuals (99%; 76–122%; P < 0.05). In parallel, fibrinolysis assessed as the overall fibrinolysis potential (OFP), part of the overall hemostatic potential assay (OHP), was decreased at all time points compared with control individuals (P < 0.01 for all) and was found to be inversely related to TAFI (r = −0.40; P = 0.0008; n = 20). The OFP and the overall coagulation potential (another part of the OHP assay), and to a lesser degree TAFI, showed significant relationships to C-reactive protein and fibrinogen. In conclusion, elevated TAFI antigen levels may be a consequence of an acute phase reaction, and together with a depressed OFP suggest impaired fibrinolysis in patients with acute ischemic stroke. The OHP method may be useful as a complement to standard hemostatic variables in evaluating hemostasis in stroke patients.