Background: The larger fraction of infant mortality is that of neonatal; and early neonatal death is the most significant contributor of neonatal mortality as a whole. There are various factors which may be associated with early neonatal mortality and they have been the reasons for the wide variation in mortality rates among the health facilities reporting.Objective: This study was made to assess the independent predictors of early neonatal mortality.Methods: From 2001 through 2005, a total of 3789 live born neonates, who were admitted to the neonatal intensive care unit of Tikur Anbessa Hospital, were included in this study. Variables were classified into two: Socio economic/reproductive factors and maternal/newborn factors. Predictors were assessed using a multivariable binary logistic regression. Variables with a p-value of <0.05 were entered into a multivariable logistic model.Results: From the socio-economic/reproductive variables: age less than one day (AOR=2.53 95% CI= (1.66, 3.85)), having three or more siblings (AOR=2.04, 95% CI= (1.15, 3.64) ), second birth order (AOR=1.79, 95% CI= (1.28, 2.51)), absence of antenatal care (AOR=1.70, 95% CI= (1.28,2.26)), and being unmarried (AOR=1.55 95%CI= (1.20,2.00)) were independent predictors of increased mortality. On the other hand, singleton pregnancy was found to be protective by 30% against early neonatal mortality with an odds of 0.70, 95% CI of (0.54, 0.90). From the neonatal/ maternal variables: gestational age of <32 weeks (AOR= 10.46, 95% CI= (5.39, 20.31)), first minute APGAR of three or less (AOR=2.12, 95% CI= (1.39, 2.23)), presence of any congenital anomaly ( AOR=2.02, 95% CI=(1.33,2.51)), presence of peri-natal asphyxia (AOR=1.82, 95% CI=(1.32,2.51)), any oxygen treatment (AOR=2.65, 95% CI=(1.89,3.72)), birth weight less than 1500 (AOR=9.64, 95%CI=(3.32,27.97)) were independent predictors of neonatal mortality. A normal weight at admission was protective of early neonatal mortality.Conclusion: There are many factors that could have influenced neonatal mortality in the current study. Antenatal care follow up is the key point of contact for planning and managing labor and delivery; it should be improved to control most other variables. The care provided to these high risk babies should also be maximized to reduce mortality in these risk groups