Background: Neonatal hypothermia is a worldwide problem and an important contributing factor to neonatal morbidity and mortality especially in low and middle income countries. Over 1.1 million neonatal deaths occur in sub-Saharan Africa and hypothermia is one of the major factors for this mortality. A global burden of neonatal hypothermia indicates 53% of Ethiopian newborns developed hypothermia due to different neonatal, obstetric and environmental related factors. Therefore, identifying the factors in Debre Markos comprehensive specialized Hospital will have importance for improving newborn survival through appropriate thermal care. Objective: To determine the prevalence of neonatal hypothermia within six hours of delivery and associated factors among neonates delivered in Debre Markos comprehensive specialized Hospital, Amhara region, North West, Ethiopia 2021. Methods and materials: An institutional based cross sectional study was conducted at Debre Markos comprehensive specialized Hospital from March 22/3/2021 to May 22/5/2021 and a total of 403 new borns were included. Axillary temperature was measured by a calibrated digital thermometer within six hours of delivery. Data were coded and entered into Epi-data (version 3.1) and exported to SPSS (version 25) software. Bivariable binary logistic regression analysis was carried out to identify factors that were associated with neonatal hypothermia and become candidate for multivariable binary logistic regression analysis at P (<0.25). Multivariable binary logistic regression analysis was performed to investigate independent associated factors by controlling possible cofounders and statistical significance was confirmed at P< 0.05. Result: The prevalence of neonatal hypothermia was 62.8% with 95% CI (58.1-67.2). This study found that low birth weight of the neonate at birth (AOR=3.07, 95%CI: 1.60, 1.89), didn’t initiation of breast feeding within one hour (AOR=3.43, 95%CI: 2.14; 5.49), didn’t got skin to skin contact (AOD=2.14, 95%CI: 1.36,3.39),Cardiopulmonaryresuscitation(AOR=3.31,95%CI:1.18,9.32) and didn’t wear cap (AOR=1.61,95%CI:1.02,2.55) had significant association with hypothermia. Conclusion and recommendation: The current magnitude of Neonatal hypothermia in the study area was relatively lower than the ones in the previous studies done in Ethiopia. Pulmonary Resuscitation of new born at birth, low birth weight of new born at birth, and delayed initiation of breast feeding, not taking skin to skin contact with mother and didn’t wearing cap were independent predictors of neonatal hypothermia. Therefore Attention is needed for thermal care of low birth weight babies and strength early initiation of breast feeding.