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Seble Mesfin,1 Mekbeb Afework,2 Dereje Bikila,3 Alemayehu Tessema,4 Midekso Sento1 1Department of Biomedical Science, Adama Comprehensive Specialized Hospital Medical College, Adama, Eastern Ethiopia; 2Department of Anatomy, School of Medicine, College of Health science, Addis Ababa University, Addis Ababa, Ethiopia; 3Department of Nursing, Arsi University College of Health Science, Assela, Ethiopia; 4Department of Pediatrics, Adama Comprehensive specialized Hospital Medical College, Adama, Eastern EthiopiaCorrespondence: Seble Mesfin; Mekbeb Afework, Tel +983501666 ; +911411285, Email seblemesfin87@gmail.com; m.afework@yahoo.comBackground: Vernix caseosa is a complex proteolipid material synthesized partly by fetal sebaceous glands during the last trimester of pregnancy. Understanding the structure and function of newborn skin is crucial for determining optimal thermal support, infection control, and skin moisturization. So far, in Ethiopia, there is no research done related to the distribution of vernix caseosa and associated factors on newborn skin. Doing such research could give awareness about factors associated with the distribution of vernix caseosa on newborns’ skin and to take necessary protective measures for those that may be affected.Objective: The objective of this study is to assess the distribution of vernix caseosa and associated factors among newborns delivered at Adama Comprehensive Specialized Hospital Medical College from November to December 1, 2021.Methodology: Hospital-based cross-sectional study design was conducted from November to December 1, 2021 at Adama Comprehensive Specialized Hospital Medical College (ACSHMC). Four hundred twenty-two eligible newborns were selected by a systematic sampling method. Data were collected by four data collectors by using a pretested questionnaire. The distribution of vernix caseosa on the different regions of the neonate was assessed, by exposing their whole body for a minute. Data entry was done by EPI data version 4.6 and analyzed by using SPSS version 25. A logistic regression of P-value of < 0.25 during bivariate and P < 0.05 during multivariate analysis at a 95% confidence level was considered statistically significant.Results: Out of 422 study participants 231 (54.7%) with 95% CI (49.8, 59.8) babies had vernix caseosa. Being primiparous with (AOR = 1.9, PV = 0.013, 95% CI: 1.141, 2.92), being multiparous with (AOR = 1.98, PV = 0.04, CI: 1.29, 3.225), being females with (AOR = 2.1, PV = 0.001, CI: 1.39, 3.18), being preterm with (AOR = 2.98, PV = 0.036, 95% CI: 1.08, 10.72), non-diseased newborns with (AOR = 1.6, PV = 0.046, 95% CI: 1.07, 2.7) were identified as associated factors for the distribution of vernix caseosa on the newborn skin.Conclusion: This study showed that the distribution of vernix caseosa on the skin of the newborns was associated with parity, sex, gestational age, and absence of disease.Keywords: epidermal barrier, stratum corneum, vernix caseosa