Introduction: Addressing the target of sustainable development goals (SDG) of reducing perinatal mortality was still a global challenge. Especially the magnitude of newborn death in the first three days of life takes major role in developing countries including Ethiopia. This study aims to determine the incidence and risk factors of new-born mortality in the first three days among babies delivered in referral hospitals of Amhara Regional state, North-Western Ethiopia.

Methods: A prospective cohort study design was conducted among 810 early neonates in the first three days between March 1, 2018, and August 30, 2018, were included. Data was entered into Epi-Data version 4.4 and analysed using to STATA™ version 14.1 for the analysis.

Result: Women who came between 17 and 28 weeks of gestation for the first visit AHR 1.67 [95% C.I 1.02, 2.73] as compared to those who start the initial antenatal care visit before 16 weeks of gestation, those not monitored with parthograph during labor AHR 2.66[95% C.I 1.70, 4.15], direct admission was 39% less risk of newborn mortality AHR .61[95% C.I .38, .97], experiencing post-partum haemorrhage were AHR 2.88[95% C.I 1.69, 4.89], developing fistula in the first 24 hours AHR 3.75[95% C.I 1.23, 11.43],  obstructed labour AHR 2.14[95% C.I 1.35, 3.38] and less than 1-hour maternal first delay to visit health facility was 39% less risk of new-borns death AHR .61[95% C.I .37, .98] were found to be significant risk factors of new-born mortality in the first three days.

Conclusion: About 1 in 7 new-borns were died in the first three days of life. Maternal risk factors (women who came between 17 and 28 weeks of gestation for the first visit and more than 1-hour maternal first delay), health system related risk factors (mothers not monitored using parthograph during labor, admission by referral from other health facility), and obstetric risk factors(mothers experiencing post-partum haemorrhage, and those develop fistula in the first 24 hours, obstructed labour for new-borns mortality) were found to significant risk factors for new-born mortality in the first three days.

Key Words: Newborn; Incidence; Risk factors; Mortality; Ethiopia