OBJECTIVE: The objective of the study was to examine the birthweight at which risks of perinatal death, neonatal morbidity, and cesarean delivery begin to rise and the causes and timing (antenatal, early or late neonatal, or postneonatal) of these risks. STUDY DESIGN: This was a cohort study based on 1999-2001 US-linked stillbirth, live birth, and infant death records. Singletons weighing 2500 g or larger born to white non-Hispanic mothers at 37-44 weeks of gestation were selected (n = 5,983,409). RESULTS: Infants with birthweights from 4000 to 4499 g were not at increased risk of mortality or morbidity vs those at 3500-3999 g, whereas those 4500-4999 g had significantly increased risks of stillbirth, neonatal mortality (especially because of birth asphyxia), birth injury, neonatal asphyxia, meconium aspiration, and cesarean delivery. Births at 5000 g or larger had even higher risks, including risk of sudden infant death syndrome. CONCLUSION: Birthweight greater than 4500 g, and especially greater than 5000 g, is associated with increased risks of perinatal and infant mortality and morbidity.