Background: Symptomatic intracranial atherothrombotic stenoses (ICAS) are associated with high rates of cerebrovascular ischemic events. Objective: To conduct a prospective multicenter study to evaluate the natural history of ICAS and, in those patients refractory to medical treatment, the outcomes associated with intracranial angioplasty. Methods: Patients aged 18 to 80 were enrolled with symptoms attributed to a single ICAS of ≥50%. Optimal medical therapy of vascular risk factors and preventive antithrombotic therapy were at the discretion of the local investigator. Patients were eligible for intracranial angioplasty after experiencing recurrent stroke despite medical therapy. Neurologic and ultrasonographic examinations were performed at study inclusion, 3 months after enrollment, and every 6 months of follow-up thereafter, for 36 months. Results:One hundred two patients were included, with a mean age of 63.3 ±10.4 years. Intracranial artery stenoses involved the vertebral artery in 22.5%, the basilar artery in 25.5%, the middle cerebral artery in 26.5%, and the internal carotid artery in 25.5%. In 27.4%of the patients, the stenoses had clinical hemodynamic characteristics. During a mean follow-up of 23.4 months, 38.2%of the patients had a cerebrovascular event: ischemic stroke in 13.7%and TIA in 24.5%. Among patients with a hemodynamically significant stenosis, 60.7%had a recurrent stroke or TIA in the territory of the stenotic artery; this association was significant in univariate analysis.Twenty-eight patients underwent an endovascular procedure with a neurologic periprocedural complication rate of 14.2%.The overall vascular death rate was 8.8%. Conclusions: Despite medical treatment, the 2-year recurrence rate of ischemic events in the territory of the stenotic artery was 38.2%. Cardiovascular events occurred in 18.6%of patients. Clinically significant hemodynamic stenoses were associated with stroke recurrence and may help identify a high risk subset of patients. Background: Symptomatic intracranial atherothrombotic stenoses (ICAS) are associated with high rates of cerebrovascular ischemic events. Objective: To conduct a prospective multicenter study to evaluate the natural history of ICAS and, in those patients refractory to medical treatment, the outcomes associated with intracranial angioplasty . Methods: Patients aged 18 to 80 were enrolled with symptoms attributed to a single ICAS of ≥50%. Optimal medical therapy of vascular risk factors and preventive antithrombotic therapy were at the discretion of the local investigator. Patients were eligible for intracranial angioplasty after experiencing recurrent stroke despite medical therapy. Neurologic and ultrasonographic examinations were performed at study inclusion, 3 months after enrollment, and every 6 months after follow-up thereafter, for 36 months. Results: One hundred two patients were included, with a mean age of 63.3 ± 10.4 years. Intracranial artery stenoses involved the vertebral arter y in 22.5%, the basilar artery in 25.5%, the middle cerebral artery in 26.5%, and the internal carotid artery in 25.5%. In 27.4% of the patients, the stenoses had clinical hemodynamic characteristics. During a mean follow-up of 23.4 months, 38.2% of the patients had a cerebrovascular event: ischemic stroke in 13.7% and TIA in 24.5%. Among patients with a hemodynamically significant stenosis, 60.7% had a recurrent stroke or TIA in the territory of the stenotic artery; this association was significantly in univariate analysis. Twenty-eight patients underwent an endovascular procedure with a neurologic periprocedural complication rate of 14.2%. The overall vascular death rate was 8.8%. Conclusions: Despite medical treatment, the 2-year recurrence rate of ischemic events in the territory of the stenotic artery was 38.2%. Cardiovascular events occurred in 18.6% of patients. Clinically significant hemodynamic stenoses were associated with stroke recurrence and may help identify a high risk subset of patients.