Background and Aim: Until now, there has been no established evidence about the best technique to predict failure of extubation. The aim of this study was to assess the occurrence rate of extubation and weaning failure, its risk factors, and predictors in pediatric intensive care unit (PICU) mechanically ventilated children. Methods: This was an observational prospective study that included 60 mechanically ventilated children in the PICU of Benha University Hospital who were subjected to mechanical ventilation (MV) for at least 48 hours. The included children were subjected to a complete clinical and laboratory evaluation. Data regarding MV were collected on admission and 24 hours prior to the trials of spontaneous breathing. Patients were categorized into a group with weaning success and another group with failure of weaning. Results: Most cases (63.3%) were weaned successfully, the most common cause of weaning failure was laryngeal edema and excessive secretion, followed by encephalopathy, hemodynamic unstable, accidental extubation, sedation. Weaning failed group had lower hemoglobin, hematocrit, lymphocytes and statistically higher neutrophils, NLR and C-reactive protein, higher MV settings compared to the weaning success group. Multivariate regression analysis showed that hemoglobin, NLR, PIP, PEEP, FIO2, sedation use, number of spontaneous breathe trial and duration of MV were independent predictors of weaning. Conclusion: Successful extubation was associated with gradual weaning. Predictors of failed weaning were anemia, low lymphocytic count, high NLR, abnormal ABGs, and high ventilatory settings on MV.