Cranial magnetic resonance imaging (MRI) of 31 newborn infants treated with venoarterial cardiopulmonary bypass for severe but reversible respiratory failure, revealed major focal parenchymal lesions in 7 of 31 infants (23%) and demonstrated abnormal enlargement of extra-axial and ventricular cerebrospinal fluid spaces in 16 of 31 (51%). No preferential left versus right lateralization of focal injury was observed in conjunction with right common carotid artery and jugular vein ligation. No statistically significant relationships were found between major brain lesions on MRI scans and the clinical characteristics of the pre-extracorporeal membrane oxygenation (ECMO), ECMO, and post-ECMO course. Major focal brain lesions were significantly associated with an asymmetric cerebrovascular response to carotid ligation of the right versus left middle cerebral arteries as detected by magnetic resonance angiography (P < .05). Enlarged cerebrospinal fluid spaces were not significantly related to the presence of parenchymal MRI lesions, but were associated with lower Bayley neurodevelopmental scores for mental (MDI) and psychomotor evaluations (PDI) at 6 and 12 months (P < .05). It is concluded that asymmetries of cerebral vascular adaptation detected by magnetic resonance angiography after ECMO may be associated with major brain lesions revealed by MRI. Thereafter, the presence of enlarged cerebrospinal fluid spaces on MRI is associated with a poor shortterm developmental outcome.