Background: Early neonatal death is a serious concern, both in the developing and developed worlds. Early neonatal death remains a health problem and is the biggest component of the neonatal mortality rate. Therefore, substantial reduction in early neonatal mortality is a crucial pre-requisite for achieving further gains in child survival in the country. However, the distribution of deaths in the community within the first week is poorly understood. Therefore, this study was conducted to assess time to death and its predictors among early neonates in the neonatal intensive care unit of Dessie Referral Hospital. Method: A retrospective cohort study was conducted in the early neonatal patient in Dessie referral hospital on the total sample size of 416 selected patients by using a simple random sampling technique. Data were collected by document review. Life table used to estimate the probability of survival, log-rank test to compare survival in two or more groups and the Cox proportional hazard model was used to determine factors associated with time to death of early neonate. The hazard ratio with 95% confidence level was used to declare statistical significant association. Result: A total of 416 early neonates were included in the study. There were 224(53.8%) male neonates. The overall early neonatal mortalities were 47(11.3%), of which 23.41% of them died on the first day of age. early neonatal mortality was associated with neonatal sepsis (AHR=3.349,95% CI,1.842-6.089), low birth weight of neonates (AHR=3.563%,95% CI,1.925-6.595), unable to breastfeeding during delivery (AHR=4.094,95% CI,1.603-10.452), neonatal respiratory distress (AHR=4.018,95% CI,1.733-9.371), perinatal asphyxia (AHR =2.540,95% CI,1.186-5.847). Conclusion: The causes of early neonatal death described in this study were preventable. Managing low birth weight, initiating exclusive breastfeeding, refining quality of service, and confirming the continuity of care are recommended to increase the survival of neonates.