Because earlier studies suggested that preterm infants with germinal matrix hemorrhage or intraventricular hemorrhage or both (GMH/IVH) present within the first 12 postnatal hours are at greatest risk for the development of high-grade hemorrhage and neurodevelopmental disability, we examined the risk factors for this insult among 229 neonates of 600 to 1250 gm birth weight in a multicenter study. All had echoencephalography (ECHO) within the first 11 hours and serially for the next 20 days; risk factor data were collected prospectively. Forty-three infants had GMH/IVH within the first 5 to 11 hours (mean age at ECHO 7.7 hours): 18 GMH and 21 grade II, 1 grade III, and 3 grade IV IVH. One hundred eighty-six infants did not have GMH/IVH at a mean age of 7.9 hours. Both groups of infants were similar in birth weight, gestational age, maternal risk factors, cord pH values, and surfactant therapy before ECHO. The group with early IVH had more vertex presentations than the group without early IVH (79% vs 55%, p = 0.043), less maternal tocolytic use (42% vs 60%, p = 0.029), and more vaginal deliveries (67% vs 44%, p = 0.005). In the first 21 days, severe IVH developed in 12 infants with early IVH and in 6 infants without early IVH (p < 0.001). There were more neonatal deaths (16% vs 6%, p = 0.035) and more deaths at any time during the primary hospitalization (23% vs 9%, p = 0.010) among the early IVH group than among the group without early IVH. Multivariate analysis indicated that the mode of delivery, fetal presentation, and birth weight were important and independent prognostic indicators of IVH.