Cranial ultrasound (US) examination is the screening technique of choice for assessing preexisting neurological damage in potential neonatal extracorporeal membrane oxygenation (ECMO) candidates. Currently, US evidence of intracranial hemorrhage greater than grade I in severity is a contraindication to ECMO at this ECMO center. In the current study, radiological findings were reviewed in 129 consecutive neonatal ECMO cases in an attempt to identify which pre-ECMO US findings were associated with the development of subsequent intracranial complications while on ECMO. Pre-ECMO head US, post-ECMO head US, and head computed tomography (CT) scans were reviewed retrospectively by one radiology team. Ventricular, parenchymal, and extraaxial fluid abnormalities were recorded for each case. Pre-ECMO US findings were then correlated with the subsequent development of significant intracranial radiological abnormalities noted on post-ECMO studies as well as with clinical data regarding ECMO course and outcome. Results showed that infants with evidence of severe edema or periventricular leukomalacia on pre-ECMO imaging had a 63% incidence of subsequent major intracranial complications. This represents a significantly higher risk than in candidates with a normal examination or evidence of grade I intracranial hemorrhage, subependymal cysts, or mild edema. These results suggest that infants with sonographic evidence of ischemic or anoxic damage on pre-ECMO US are at high risk for the development of significant intracranial complications if ECMO therapy is instituted.