Introduction: Acute respiratory failure (ARF) is the most common problem seen in the preterm and term infants admitted to neonatal intensive care units. Etiology is not uniform, and mostly depend on gestational age. For adequate treatment is certainly important to recognize and treat underlying disease, but at the same time, we have to supply adequate respiratory support, tissue perfusion and oxygen deliveries. For a good outcome we need reliable estimation method for functional state of respiratory system, as well as monitoring the effects of treatment. Current assessment ARF is with blood gas, chest X-ray and Oxygenation index (OI). OI is quite aggressive assessment method for neonates, because it involves arterial blood sampling. Promoted in recent studies, Oxygen saturation index (OSI) measured by pulse oximetry, attempts to objectively score respiratory disease with parameters available non-invasively. The aim of our research is to evaluate correlation between OSI and OI in neonates with ARF requiring mechanical ventilation. Material and methods: In a retrospective cohort study 101 neonates were selected, treated at the Department of intensive therapy and care, Pediatric clinic of Tuzla, due to ARF requiring mechanical ventilation. We reviewed data such as gestational age, birth weight, gender, Apgar scores, values of Score for Neonatal Acute Physiology-Perinatal Extension, all the parameters from the arterial blood gas analysis, pulse oximetry values, Oxygenation Index and Oxygenation Saturation Index, that were calculated by the formulas. OSI and OI were calculated and correlated. Mean values of OSI and OI correlated with Pearson's coefficient of 0.76; p < 0.0001 (95% CI = 0.66-0.83). OSI correlated with SNAP-PE with Pearson's coefficient of 0.52; p < 0.0001 (95% CI = 0.36-0.65). Comparing the values of OSI between patients who died and those who survived, we found that OSI correlated with the outcome with Spearman's coefficient of -0.47; p < 0.0001 (95% CI = -0.16 - -0.31). Bland-Altman plot confirmed correlation between OSI and OI in mean values, identifying discrepancy between two indices for extreme values.In conclusion, OSI correlates significantly with OI in infants with respiratory failure. This noninvasive method of oxygenation assessment, utilizing pulse oximetry, can be used to assess the severity of ARF and mortality risk in neonates.