The purpose of this study was to examine how the prognosis of patients who presented with a recent ischemic event referable to a 70% to 99% stenosis of one carotid artery (ipsilateral) was altered by stenosis and occlusion of the contralateral carotid artery. The benefit of performing carotid endarterectomy on the recently symptomatic artery, in the presence of contralateral artery disease, was also examined. A total of 659 patients were grouped into one of three categories according to the extent of stenosis in the contralateral carotid artery: less than 70% (559 patients), 70% to 99% (57 patients), and occlusion (43 patients). Strokes that occurred during the follow-up period were designated as ipsilateral if they arose from the same carotid artery as the symptom for which the patient had been entered into the study. Medically treated patients with an occluded contralateral artery were more than twice as likely to have had an ipsilateral stroke at 2 years than patients with either severe (hazard ratio: 2.36; 95% confidence interval (CI): 1.00-5.62) or mild-to-moderate (hazard ratio: 2.65; 95% CI: 1.43-4.90) contralateral artery stenosis. The perioperative risk of stroke and death was higher in patients with an occluded contralateral artery (4.0% risk) or mild-to-moderate (5.1% risk) contralateral stenosis. Regression analyses indicated that the results were not affected by other risk factors. An occluded contralateral carotid artery significantly increased the risk of stroke associated with a severely stenosed ipsilateral carotid artery. Despite higher perioperative morbidity in the presence of an occluded contralateral artery, the longer-term outlook for patients who had endarterectomy performed on the recently symptomatic, severely stenosed ipsilateral carotid artery was considerably better than for medically treated patients.