Objective: To develop and validate a model for very low birth weight (VLBW) neonatal mortality prediction, based on commonly available data at birth, in 16 neonatal intensive care units (NICUs) from five South American countries. Study Design: Prospectively collected biodemographic data from the Neonatal del Cono Sur (NEOCOSUR) Network between October 2000 and May 2003 in infants with birth weight 500 to 1500g were employed. A testing sample and crossvalidation techniques were used to validate a statistical model for risk of in-hospital mortality. The new risk score was compared with two existing scores by using area under the receiver operating characteristic curve (AUC). Results: The new NEOCOSUR score was highly predictive for in-hospital mortality (AUC=0.85) and performed better than the Clinical Risk Index for Babies (CRIB) and the NICHD risk models when used in the NEOCOSUR Network. The new score is also well calibrated - it had good predictive capability for in-hospital mortality at all levels of risk (HL test=11.9, p=0.85). The new score also performed well when used to predict in hospital neurological and respiratory complications. Conclusions: A new and relatively simple VLBW mortality risk score had a good prediction performance in a South American network population. This is an important tool for comparison purposes among NICUs. This score may prove to be a better model for application in developing countries. © 2005 Nature Publishing Group. All rights reserved.