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Background: The role of vertebral artery hypoplasia (VAH) in stroke pathophysiology is still debated. In this study, we correlated extra- and intra-cranial vertebral artery ultrasound findings with brain CT/MRI and clinical outcome., Materials and Methods: We recruited all consecutive first-ever stroke patients with a documented acute ischemic brain lesion and a complete extra-intracranial ultrasound evaluation. Those with previous stroke, or with anterior and posterior strokes were excluded. The prevalence of VAH diagnosed by ultrasound was recorded both in anterior circulation and posterior circulation infarctions. In the latter group, we compared the risk profile, topographic and neuroradiological lesion features, etiology and clinical outcome based on the presence of VAH., Results: The study included 750 patients [436 males (58%); mean age 65 years; age range 18-90] with first-ever acute ischemic stroke: 193 (25.7%) with a posterior circulation infarction, 557 (74.3%) with an anterior circulation infarction. VAH was more often detected in the former group (33.7 vs. 14.1%; p < 0.0001). Patients with posterior circulation stroke and VAH had a significantly higher frequency of basilar artery stenosis [OR 2.07 (1.00-4.26); p < 0.05], stenosis of the contralateral vertebral artery [64 vs. 36%; OR 3.22 (1.24-8.37); p < 0.05], and fetal-type variant of the posterior cerebral artery [25 vs. 13%; OR 2.17 (1.00-4.68); p < 0.05]., Conclusions: According to our study, VAH identifies patients at higher risk of posterior circulation stroke, and higher frequency of contralateral vertebral artery stenosis and basilar artery stenosis.