Background: Ethiopia has made large-scale healthcare investments to improve child health and survival. However, there is insufficient population level data on the current estimates of infant mortality rate (IMR) in the country. The aim of this study was to measure infant mortality rate, investigate risk factors for infant deaths and identify causes of death in a rural population of northern Ethiopia. Methods: Live births to a cohort of mothers under the Kilite Awlaelo Health and Demographic Surveillance System were followed up to their first birthday or death, between September 11, 2009 and September 10, 2013. Maternal and infant characteristics were collected at baseline and during the regular follow-up visit. Multiple-Cox regression was used to investigate risk factors for infant death. Causes of infant death were identified using physician review verbal autopsy method. Results: Of the total 3684 infants followed, 174 of them died before their first birthday, yielding an IMR of 47 per 1000 live births (95 CI: 41, 54) over the four years of follow-up. About 96 of infants survived up to their first birthday, and 56 of infant deaths occurred during the neonatal period. Infants born to mothers aged 15-19 years old had higher risk of death (HR=2.68, 95 CI: 1. 74, 4.87) than those born to 25-29 years old. Infants of mothers who attained a secondary school and above had 56 lower risk of death (HR=0.44, 95 CI: 0.24, 0.81) compared to those whose mothers did not attend formal education. Sepsis, prematurity and asphyxia and acute lower respiratory tract infections were the commonest causes of death. Conclusion: The IMR for the four-year period was lower than the national and regional estimates. Our findings suggest the need to improve the newborn care, and empower teenagers to delay teenage pregnancy and attain higher levels of education.