Hepatic cirrhosis is characterized by complex abnormalities of the fibrinolytic system. Little is known about the possible association between these alterations and thrombosis. The aim of this study was to evaluate the fibrinolytic profile in cirrhotic individuals with and without portal vein thrombosis (PVT). We measured thrombin activatable fibrinolysis inhibitor (TAFI), total amount of activated TAFI (TAFIa/ai), plasminogen activator inhibitor (PAI-1), plasminogen and fibrinogen plasma levels in 66 cirrhotic patients (33 with and 33 without PVT) and in 66 healthy volunteers. TAFI plasma levels (median [range]) were significantly lower in cirrhotic individuals (5.6 μg/ml [1.7-11.7]) than in controls (10.1 μg/ml [6.6-14.2], p < 0.0001), while TAFIa/ai levels were significantly higher in cases (18.3 ng/ml [0.3-35.4]) than in controls (15.9 ng/ml [7.4-41], p = 0.02). Cirrhotic patients with PVT had higher TAFI (6.6 μg/ml [2.9-10.1]), TAFIa/ai (19.2 ng/ml [11.6-35.4]) and PAI-1 (33.1 ng/ml [27.6-56.3]) plasma levels than those without PVT (3.9 μg/ml [1.7-11.7], p = 0.001; 15.6 ng/ml [10.3-33.9], p = 0.037; 15.9 ng/ml [2.5-29.1], p = 0.004. The fibrinolytic profile in cirrhotic individuals with PVT is characterized by higher levels of TAFI, TAFIa/ai and PAI-1 than in those without PVT. These alterations identify a hypofibrinolytic condition that may increase the risk of developing a thrombotic event.