Objective The purpose of this study was to examine characteristics associated with neonatal mortality among extremely low-birth-weight infants (≤1000 g). Study design A population-based, case-control study using linked Missouri birth and death certificates from 1989 to 1997 was conducted. Cases (n = 835) were defined as extremely low-birth-weight infants that died within 28 days of birth. Controls (n = 907) were randomly selected from extremely low-birth-weight infants that were alive at 1 year and were frequency matched to subjects by birth year and birth weight. Results Infants born with severe congenital anomalies and at the youngest gestational ages were at greatest risk for neonatal mortality. Other significant risk factors included maternal age ( 34 years), vaginal delivery, nontertiary hospital care, malpresentation, male gender, and small for gestational age. Black race and preeclampsia were protective against early death. Conclusions The risk of neonatal mortality among extremely low-birth-weight infants was associated with several maternal, infant, and obstetric factors, some of which may be preventable.