Unfractionated heparin (UFH) for 48 h has been the traditional standard anticoagulant with fibrinolytics. The Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction (ExTRACT)-Thrombolysis in Myocardial Infarction (TIMI) 25 trial prospectively studied the usefulness of enoxaparin and found that in patients treated with fibrinolysis, enoxaparin administered throughout the index hospitalization was superior to the standard 48-h UFH infusion. However, enoxaparin increased major bleeding. The data from this large trial were further analyzed across various subgroups and these results support the use of enoxaparin in a broad range of patients. The ExTRACT-TIMI 25 trial employed a novel dosing regimen for enoxaparin adjusted for age and renal function, which was designed to minimize bleeding risk while maintaining the beneficial effects of enoxaparin. Based on the evidence from this trial, the 2007 ST-segment elevation myocardial infarction guidelines now preferentially recommend enoxaparin to be administered throughout the index hospitalization as per the dosing regimen used in ExTRACT-TIMI 25 in most patients treated with fibrinolytic therapy.