Background Anterior circulation infarction (ACI) accounts for almost 70% of all strokes, whereas posterior circulation infarction (PCI) accounts for 20% of the strokes, with heterogeneous clinical manifestations. Objectives The aim of the present study was to compare the clinical characteristics of ACI with PCI, and to detect the diagnostic importance of specific symptoms and signs for PCI. Patients and methods We prospectively analyzed acute ischemic cerebral stroke (AICS) patients, enrolled in the study from the convalescence and critical cases of Mansoura University Hospitals (CCCB-MUH) during a 1-year period. Patients were analyzed for ischemic stroke subtypes (ACI and PCI), demographic data, risk factors, and clinical characteristics. All patients underwent an assessment by using the Glasgow Coma Scale and the National Institutes of Health Stroke Scale at the onset of AICS. Results The study included 234 patients with AICS (174 belonging to the ACI subtype; 60 to the PCI subtype). PCI patients were often men, had a higher presence of cervical spondylosis, lower mean National Institutes of Health Stroke Scale, and a lower mean Glasgow Coma Scale. PCI patients had a greater frequency of diabetes and smoking. Among the PCI patients, ataxia, vertigo, unsteadiness, nystagmus, crossed motor, and sensory deficits were statistically significant compared with the ACI patients. As regards speech disturbances, aphasia occurred in a low percentage of the PCI patients, and no statistically significant difference regarding dysarthria was found in the two groups. The neurological deficits favoring the diagnosis of PCI were nystagmus, crossed motor and sensory deficits, ataxia, vertigo, unsteadiness, diplopia, Horner's syndrome, and oculomotor nerve palsy. Conclusion There is an apparent difference in the frequency of the most common manifestations between PCI and ACI patients. Some neurological deficits were highly specific for diagnosing PCI.