Context. - The relative importance of hemodynamic factors in the pathogenesis and treatment of stroke in patients with carotid artery occlusion remains controversial. Objective. - To test the hypothesis that stage II cerebral hemodynamic failure (increased oxygen extraction measured by positron emission tomography [PET]) distal to symptomatic carotid artery occlusion is an independent risk factor for subsequent stroke in medically treated patients. Design and Setting. - Prospective, blinded, longitudinal cohort study of patients referred from a group of regional hospitals between 1992 and 1996. Patients. - From 419 subjects referred, 81 with previous stroke or transient ischemic attack in the territory of an occluded carotid artery were enrolled. All were followed up to completion of the study, with average follow-up of 31.5 months. Main Outcome Measures. - Telephone contact every 6 months recorded the subsequent occurrence of all stroke, ipsilateral ischemic stroke, and death. Results. - Stroke occurred in 12 of 39 patients with stage II hemodynamic failure and in 3 of 42 patients without (P = .005); stroke was ipsilateral in 11 of 39 patients with stage II hemodynamic failure and in 2 of 42 patients without (P = .004). Six deaths occurred in each group (P = .94). The age-adjusted relative risk conferred by stage II hemodynamic failure was 6.0 (95% confidence interval [CI], 1.7-21.6) for all stroke and 7.3 (95% CI, 1.6-33.4) for ipsilateral stroke. Conclusions. - Stage II hemodynamic failure defines a subgroup of patients with symptomatic carotid occlusion who are at high risk for subsequent stroke when treated medically. A randomized trial evaluating surgical revascularization in this high-risk subgroup is warranted.