Early stroke in the premature infant has rarely been described. Presented here are the cases of 23 infants, born between 23 and 35 weeks gestational age, with focal arterial ischemic stroke occurring before 44 weeks gestational age. Ten (43%) were male. Five children (22%) were half of a twin pair; no co-twin died. The most commonly affected territory was the middle cerebral artery territory. Three children with extreme prematurity (< or =26 weeks) had cerebellar infarcts. Twelve children had unilateral or bilateral intraventricular hemorrhages (grade 3 or higher in 8 of the 12). Twelve children had white matter injury: periventricular leukomalacia, hypoxic-ischemic encephalopathy, or both. Most children had multiple comorbidities, and the median neonatal intensive care unit stay was 63 days (range, 14-365). One child died in the neonatal intensive care unit (age 123 days). All 22 survivors were left with disabilities. Seventeen (77%) had cerebral palsy, 10 (45%) had epilepsy, and 17 (77%) had cognitive impairment. Arterial ischemic stroke appears to add to the neurologic disabilities commonly associated with prematurity.