Most studies about perinatal arterial ischemic stroke (PAIS) exclude preterm infants. In a prospectively studied hospital-based population, 42% of our 73 newborn infants with PAIS had a gestational age (GA) < or =36 weeks. PAIS was present on the left in 61% of the preterm infants and bilateral in 7%. The middle cerebral artery (MCA) was most often affected. Involvement of the lenticulostriate branches was common among preterm infants with GA of 28-32 weeks, and involvement of the MCA main branch was seen in almost all with a GA>33 weeks. Twin-to-twin transfusion syndrome, fetal heart rate abnormality and hypoglycemia were independent risk factors. No maternal risk factors could be identified. Comparing neurodevelopmental outcome, infants with a main branch MCA infarct, irrespective of being preterm or full-term, were found to be most at risk of motor/cognitive impairment. Preterm infants with PAIS had more language problems at 2 years of age.