Our objectives were to establish antecedent factors and patterns of brain injury and their prognostic value in preterm infants with hypoxic-ischemic encephalopathy (HIE). Essential inclusion criteria were gestation (GA) < or =36 wk, Apgar scores <5/<7 at 1/5 min, major resuscitation at birth, and a brain MRI <6 postnatal wk. At least one additional criterion was required of the following: abnormal intrapartum CTG, sentinel event, meconium, cord pH <7.0, neonatal seizures, and multiorgan failure. Antenatal and perinatal data and > or =2 y neurodevelopmental outcome were documented. Fifty-five infants (GA 26-36; median, 35 wk) were eligible; all had 1-6 (median, 3) additional criteria. Placental abruption was the commonest identifiable antecedent event. Evidence of infection was not prominent. Main sites of injury were basal ganglia (BG, 75%), mostly severe, white matter (WM, 89%), mostly mild, brainstem (44%), and cortex (58%). Brainstem injury was associated with severe BG, WM, and cortical injury. Two-year outcome: death (32%), cerebral palsy (26%, mostly severe quadriplegia), mild impairment (10%), and normal (32%). Significant central gray matter and brainstem injury was found in many preterm infants with HIE. Neonatal MRI findings allowed accurate prediction of neurodevelopmental outcome. Early MRI is feasible and a valuable tool in this poorly reported group of infants.