BackgroundNeonatal Nosocomial infections (NNIs) are a significant cause of morbidity and mortality for neonates in an intensive care unit. Neonatal causes of death in healthcare facilities are attributed to different factors. We aimed to investigate factors associated with NNIs, estimate the burden of NNIs, and assess how the prediction effects help to save medical mortality and length of hospital stay.MethodA prospective longitudinal study was conducted and data were collected from January 2022 to June 2022 from Jimma University Medical Center (JUMC). The data were gathered in a variety of ways, including an in-person interview with the patient’s caregiver, direct observations of neonatal patients, and a review of the study participants’ charts. This study includes patients aged 3 to 28 days who were admitted to the JUMC neonatal ward and stayed for at least 48 h. Multi-state model formulation and multivariate logistic regression were used for data analysis.ResultsA total of 545 neonates were included out of 688, and 30% (n = 164) of them acquired nosocomial infections (NIs); 98 (33%) of infected patients were born prematurely; and 71 (31.4%) were underweight at birth. NIs were higher in neonates with long hospital stay (AOR: 1.16, 95%CI: 1.13–1.20), use of urinary catheters (AOR: 3.09, 95%CI: 1.55–6.15), and undergoing surgical procedures (AOR: 2.42, 95%CI: 1.13–5.17). Patients who developed NIs had a higher risk of death (HR: 2, 95% CI: 1.31, 3.04). The burden of neonatal NIs was determined to have a risk of 0.3, a mortality rate of 9.6%, and an average duration of hospital stay of 14.6 days. Competing risk regression suggests that neonates with NIs have a significantly higher risk of death than those who are not infected (HR: 16.42, 95% CI: 8.70-30.98, p < 0.001). Assumed prevention that decreases the NIs rate in half would result in 101 lives and 1357 patient days saved from 10,000 neonatal inpatients.ConclusionUrinary catheterization and surgical procedure increased neonatal NIs. Longer hospital stay can increase the risk of NIs and can also result from the NIs. Our finding indicated that effective prevention of NIs could help reduce neonatal deaths and their hospital stays.