Population studies can help identify the complex set of risk factors for neonatal mortality among very low birth weight infants. A cohort (2000-2001) of 213 live newborns with birth weight < 1,500g in the southern region of São Paulo city, Brazil, was studied (112 neonatal deaths and 101 survivors). Data were obtained from home interviews and hospital records. Survival analysis and multiple Cox regression were performed. The high mortality in the delivery room and in the first day of life among neonates < 1,000g and < 28 weeks gestational age and the absence of survival in neonates < 700g suggest that care was actively oriented towards newborns with better prognosis. Increased risk of neonatal mortality was associated with maternal residence in slum areas, history of previous cesarean(s), history of induced abortion(s), adolescent motherhood, vaginal bleeding, and lack of prenatal care. Cesarean section and referral of the newborn to the hospital nursery showed protective effects. Birth weight less than 1,000g and Apgar index < 7 were associated with increased risk. The high mortality was due to poor living conditions and to maternal and neonatal characteristics. Improvement in prenatal and neonatal care could reduce neonatal mortality in these infants.