Background: The role of transcranial grayscale ultrasound (TC-GSUS) and transcranial color Doppler (TCD) in the diagnosis and prognosis of neonatal hypoxic-ischemic encephalopathy (HIE) is still questionable. Objective: This study targeted to evaluate the role of TC-GSUS and TCD in diagnosis and prediction of the outcome of neonates with suspected HIE in comparison to Sarnat's clinical scoring. Patients and methods: 26 neonates with suspected HIE were clinically evaluated and the severity of HIE was categorized according to Sarnat's clinical staging. Then, all neonates underwent sonographic examinations. TC-GSUS was performed at levels of anterior, mastoid, and posterior fontanelles and the level of the temporal window. Results: Cranial biometry had negative and positive rates for HIE of 7.7% and 92.3%, respectively. Using TC-GSUS, periventricular leukomalacia, intraventricular hemorrhage, brain edema, and hydrocephalus were detected in 17, 19, 14, and 16 patients, respectively. According to the resistive index (RI) of intracranial vessels, TCD excluded HIE in 11 patients and assured diagnosis of HIE with varying severity in 15 patients. Five neonates died and four developed neurological affection during follow-up. The outcome was correlated with Sarnat's scoring, ventricular-hemispheric ratio, and abnormalities of RI. Statistical analyses defined severity of HIE as judged by RI as the significant predictor for mortality and abnormal RI of anterior cerebral (ACA) and internal carotid arteries (ICA) are the most significant predictors of outcomes. Conclusion: TCD can diagnose HIE in neonates with high sensitivity and specificity and abnormal RI of ICA and ACA might be used as valuable diagnostic and prognostic tests.