The hyperperfusion syndrome is a rare delayed postoperative complication of carotid endarterectomy (CEA) characterized by headache and seizure, with or without intracranial edema or hemorrhage. Between January 1996 and December 2003, 1,602 CEAs were performed. Six patients (0.4%) developed symptoms of hyperperfusion within 2 weeks of surgery. All patients had critical stenoses, five > or =90% and one 80-90%, with poor backbleeding from the distal internal carotid artery noted at operation in all cases. Five patients were asymptomatic prior to operation; one had a hemispheric transient ischemic attack. Three patients had severe contralateral internal carotid disease (two occlusions and one severe stenosis). Two patients developed severe, self-limiting headache that prolonged hospitalization. Three patients had ipsilateral intracranial bleeding, two occurring after an uneventful postoperative course. After initial discharge from the hospital, severe intracranial hemorrhage caused death in two patients. One patient experienced focal seizures 1 week after discharge. Hypertension did not appear to be related to the symptoms in any case. During the study period, the hyperperfusion syndrome caused three of five perioperative strokes (60%) and two of seven deaths (29%) in the entire endarterectomy population. Although rare, the hyperperfusion syndrome accounts for a significant percentage of the neurological morbidity and mortality following CEA.