Abstract Background: The most frequent disorders of admission in neonatal intensive care unit is respiratory distress syndrome. Continuous positive airway pressure (CPAP) is essential to maintains functional residual capacity. Many predictors of CPAP failure have been reported in studies Aim of Study: This study aimed to evaluate the early predictors of the failed continuous positive airway pressure (CPAP) in preterm babies with respiratory distress syndrome (RDS). Patients and Methods: All born preterm neonates with gestational age (GA) 36 weeks or less from December 2020 to October 2022, in whom CPAP was initiated within the first 72 hours after birth and FIO2 level was determined in the first 2 hours of life, were enrolled in the study. Results: Of the 207 neonates 36 weeks gestation or less in the study, 7 neonates were excluded from the analysis, so 200 neonates were included. In the vast majority of neonates with CPAP failure, the following factors were highly significant explaining CPAP failure as birth weight and FiO2 level at the first & second hours of life compared to CPAP success patients. In ROC analysis, FiO2 - 1st hr. at cut off point >0.38 and FiO2 - 2nd hr. at cut off point >0.33 achieved significance for predicting CPAP failure with sensitivity of (72%, 87%) and specificity of (66.7%, 70.2%), with PPV (68%, 79%) and NPV (70%, 82%), respectively. Conclusion: FiO2 - 1st hr> 0.38 and FiO2 - 2nd hr. >0.33 predict CPAP failure in preterm neonates.