Background: Critically ill full-term infants are at risk for brain injury.The improvement of the survival of the “High-Risk Neonate" requires early detection of neurological abnormalities. Cranial ultrasonography (CUS) is the preferred tool to study the neonatal brain. Objective: This study aimed to evaluate the diagnostic role of cranial US in high-risk full-term neonates. Patients and Methods: This observational study was conducted on 60 high-risk full-term neonates randomly selected from the Neonatal Intensive Care Unit, Pediatric Department, Benha University Hospitals. Detailed history, clinical examination, appropriate investigations and cranial ultrasound were done. Results: The cranial ultrasound findings were normal in 58 cases (96.7%) and abnormal only in 2 cases (3.3%). The cranial ultrasound abnormalities found in the first case that was diagnosed as hypoxic ischemic encephalopathy and congenital malformation were hypoplasia of the cerebellar hemispheres, dilated fourth ventricle and prominent cisterna magna with Dandy walker malformation. The second case who was diagnosed as pneumonia and neonatal sepsis, cranial sonography showed cystic leukomalacia and communicating hydrocephalus. Conclusion: Although we found only 2 cases (3.3%) with abnormal CUS among the studied high-risk full-term neonates, cranial ultrasound is considered an important noninvasive method for brain imaging in neonates especially in those presented with neurological manifestations or exposed to hypoxia. It enables screening and follow up of the brain by serial imaging.