Background: Non-invasive ventilation (NIV) refers to methods of respiratory assistance without an indwelling endotracheal tube. Objectives: To evaluate the efficacy, identify possible predictors for the success of NIV in preventing intubation and re-intubation, and to determine the characteristics, and outcomes associated with NIV therapy in Pediatric intensive care units (PICUs) settings. Patients and Methods: A clinical trial study was conducted at the Pediatric Intensive Care Units, Children Hospital, Zagazig University and Al-Ahrar Educational Hospital on 60 patients divided equally into two groups; group A with NIV as the first line and group B with NIV after extubation. Patients were followed up till weaning. Results: Male constituted a larger percentage with both groups. One-sixth and 20% of patients within group A and B respectively had failed to wean. There is a statistically significant difference between the outcome of weaning among group A and all of PIM-2 score, PIM-2 percent, and NIV duration. While the relation is significant between the outcome of weaning among group B and patients’ age, body weight, and NIV duration. Increasing NIV duration significantly predicts weaning success in group A while increasing body weight predicts it in group B. Conclusion: Non-invasive ventilation as the first line of treatment in acute respiratory failure provides significant avoidance of intubation and lowers the incidence and risk of complications. Non-invasive ventilation if considered after weaning of invasive mechanical ventilation it helps to avoid re-intubation and failure of weaning. The most important significant predictors of NIV outcome are NIV duration and body weight.