A randomized trial of immediate versus delayed anticoagulation of patients with cardiogenic embolic brain infarction was carried out in a multi-centered study. Patients who were within 48 hours of onset of deficit and who had no evidence of hemorrhage on computed tomography (CT) were randomized to receive either immediate heparinization or no anticoagulants for the initial 14 days following Stroke. There were 63 patients with embolic stroke identified during the study period. Eighteen patients were not randomized because of specific exclusion criteria or delayed identification more than 48 hours after Stroke. Of 45 patients who were randomized, 44 patients (98%) completed the initial week of the protocol: 24 were immediately heparinized at an average of 32 hours after stroke, 21 received no immediate anticoagulation. Two patients developed delayed hemorrhagic infarction and two patients experienced early recurrent embolism, all among the nonanticoagulated group. Of all patients with embolic stroke who were not receiving coumadin at onset of stroke, only two of 56 (4%) had hemorrhagic infarction on initial CT. Follow-up CT in 40 of these patients showed late developing hemorrhagic infarction in two additional patients (5%). All four hemorrhagic infarctions occurred in 18 non-anticoagulated patients with large infarcts. There were no major complications associated with immediate heparinization of 24 unselected patients with all sizes of embolic infarction. A trend toward reduction of early recurrent embolism was apparent. These data support immediate anticoagulation of nonhypertensive patients with embolic brain infarction who have no evidence of hemorrhage on CT performed 24–48 hours after Stroke.