The goal of this study was to determine the prevalence and pattern of pre-operative brain injury in infants with transposition of the great arteries (TGA) compared with other complex congenital heart disease (CHD) and to define the risk of balloon atrial septostomy (BAS) for the development of brain injury.It has recently been suggested that infants with TGA are at increased risk of pre-operative brain injury, in particular, stroke, and that this is strongly associated with having a BAS.Sixty-four newborn infants with TGA (n = 44), hypoplastic left heart syndrome (n = 13), or pulmonary atresia (n = 7) had magnetic resonance imaging (MRI) scans performed before surgery.Thirty-three (75%) of the infants with TGA had a BAS. Brain injury occurred in 19 (30%) infants: white matter injury (WMI) in 17 (27%), and stroke in 3 (5%). There was no difference in the prevalence or pattern of brain injury between diagnostic groups. There was no association between BAS and brain injury in infants with TGA. There was a trend toward increased brain injury in TGA with an intact interventricular septum compared with TGA with a ventricular septal defect (38% vs. 8%, p = 0.075). There was no association between brain injury and any clinical variables.Pre-operative brain injury on MRI scan was present in 30% of infants with CHD. The predominant pattern was WMI. The rates and patterns of pre-operative brain injury are similar in infants with TGA compared with other complex CHD, and BAS does not increase the risk of pre-operative brain injury.