Background: Head US, the cornerstone neuroimaging modality in neonates, is believed to be less sensitive than MRI for detecting hypoxic ischemic injury (HII). Most reports comparing these modalities are retrospective and have a long interval between the exams. Objective: To prospectively characterize the range of abnormalities found in US examinations performed within 2 h of brain MRI in encephalopathic neonates. Materials and methods: A total of 76 consecutive exams met our inclusion criteria. Diagnostic performance of the US images was prospectively compared with MRI. Results: MRI was considered positive for HII in 53 neonates. Of the remaining 23, MRI was negative for HII in 9, showed white matter abnormalities unrelated to HII in 8, and was inconclusive in 6. Of the 70 neonates with conclusive examinations, the US exam was regarded as positive in 67. Diagnostic accuracy of US was 95.7%. Conclusion: Our study demonstrates that US should still be regarded as a screening test in neonates. US is more sensitive for the detection of injury than previously reported, and more attention should be paid to proper US technique. MRI shows disease more extensively and should be accomplished as early as possible.