Background and Purpose-The purposes of this study were to evaluate and review the risk factors and clinical features of patients with posterior circulation stroke involving mesencephalon and neighboring structures and to describe the clinical syndromes according to the mesencephalic arterial territory involved. Methods-We studied all patients with acute posterior circulation stroke involving mesencephalon who were admitted consecutively to our stroke unit over a 6-year period. We selected these patients (3%) from 1296 patients with posterior circulation infarct. Neurological and radiological investigations, including MRI and angiography, were performed in all cases. We classified patients into 4 groups on the basis of MRI findings: (1) isolated mesencephalic infarcts (9 patients); (2) distal territory infarcts (19 patients), including mesencephalon, thalamus, medial temporal and occipital lobes, and cerebellum; (3) middle territory infarcts (12 patients), including the pons and anterior inferior cerebellar artery territory; and (4) proximal territory infarcts (1 patient), including the medulla and posterior inferior cerebellar artery territory. Results-Middle mesencephalon involvement was the most common in all groups, and the anteromedial territory was frequently affected, depending on the direct perforators of basilar artery. In patients with isolated mesencephalic infarct, the clinical picture was dominated by nuclear or fascicular third-nerve palsy and contralateral motor deficits. The distal territory involvement was the most common and associated with consciousness disturbances, gait ataxia, ocular motor disturbances, and visual field deficits. The neurological picture of middle territory infarcts was dominated by consciousness disturbances with dysarthria, horizontal ocular motor disorders, and hemiparesis. Proximal territory involvement was rare and associated with acute unsteadiness, vertigo, dysphagia, dysphonia, tetra-ataxia, and motor weakness. The most common cause of stroke was large-artery disease in 16 patients (39%), cardioembolism in 8 (20%), and small-artery disease with lacunar mesencephalic infarct in 10 (24%). Bilateral mesencephalic infarcts were not uncommon (27%), mainly in patients with multiple and extended infarcts in the posterior circulation, and were associated with poor outcome compared with unilateral infarct. Conclusions-Our study highlights the topographic and clinical heterogeneity of the acute posterior circulation infarcts involving mesencephalon. The variety of the underlying potential causes of stroke requires detailed investigations of the extra and intracranial arteries and the heart.