Thrombotic and hemorrhagic complications are frequent in patients with essential thrombocythemia (ET), a myeloproliferative syndrome with an increased number of circulating platelets. Since platelets are a physiological reservoir for the plasminogen activator inhibitor (PAI-1) contained in plasma, we evaluated plasma and platelet tissue plasminogen activator (tPA) and PAI-1 in 20 ET patients with and without thrombotic complications and in 13 control subjects. In ET patients with thrombotic complications there was a significantly greater platelet PAI-1 functional activity than in ET patients without thrombotic complications and in the control group (p < 0.05 and p < 0.025, respectively). Moreover, platelet tPA activity was significantly low in all ET patients (p < 0.001). This fibrinolytic imbalance (increased plasminogen inhibitor and lowered activator) might be a critical cofactor in the thrombotic complications in ET patients.