ObjectiveThis study aimed to assess the magnitude of preterm neonatal mortality in hospitals and associated factors in northern Ethiopia.DesignInstitutional-based cross-sectional study.SettingComprehensive specialised hospitals in the Tigray region, northern Ethiopia.ParticipantsPreterm neonates admitted in Ayder and Aksum comprehensive specialised hospitalsPrimary outcomeMagnitude of preterm neonatal mortality.Secondary outcomeFactors associated with preterm neonatal mortalityResultThis study was conducted from 1 April 2019 to 15 May 2019 among 336 participants with a response rate of 96.8%. The magnitude of preterm neonatal mortality was 28.6% (95% CI: 24.0 to 33.7). In multivariable logistic regression, respiratory distress syndrome (adjusted odd ratio (AOR)=2.85; 95% CI: 1.35 to 6.00), apnoea of prematurity (AOR=5.45; 95% CI: 1.32 to 22.5), nulli parity (AOR=3.63; 95% CI: 1.59 to 8.24) and grand parity (AOR=3.21; 95% CI: 1.04 to 9.94) were significant factors associated with preterm neonatal mortality. However, receiving Kangaroo mother care (AOR=0.08; 95% CI: 0.03 to 0.20) and feeding initiated during hospitalisation (AOR=0.07; 95% CI: 0.03 to 0.15) were protective against preterm neonatal mortality.ConclusionsThe magnitude of preterm neonatal mortality in hospitals was still high. Interventions geared towards curbing preterm in-hospital neonatal mortality should strengthen early diagnosis and treatment of preterm newborns with respiratory distress syndrome and apnoea of prematurity; while concomitantly reinforcing the implementation of kangaroo care and early feeding initiation is important.