Introduction: Weaning from mechanical ventilation is defined as the gradual process of transferring the respiratory work of breathing from the ventilator to the patient. It is easily obtained in about 70-80% of the patients. However 20–30% present with difficult weaning. Aim of the work: To identify the causes of difficult weaning from mechanical ventilation of different reasons and predicts the variables responsible for this difficulty. To avoid these variables and decreasing the mortality, the morbidity associated with mechanical ventilation. Patients and methods: This study was a prospective study, which conducted on fifty (50) ventilated critically ill children, 23 (46%) male, and 27 (54%) females their ages ranged from 4-15 months of different reasons in the pediatric intensive care unit of Al-Hussein 20 (40%) Al-Azhar University Hospital, and Benha Children Hospital (BENCH) 30 (60%) during the period from July 2015 to June 2017. Results: Increasing duration of mechanical ventilation more than 7days increases risk for difficult weaning. Regarding risk factors for failure of weaning, percentage of Pneumonia was significantly lower among simple weaning than difficult weaning (30.0%, 65.0% respectively) p=0.021 Convulsions due to hypoxic ischemic insult one of most common causes of difficult weaning, anemia ,heart failure, laryngeal edema have a rule in difficult weaning.Conclusion: Increasing duration of mechanical ventilation more than 7days increase risk for difficult weaning. Percentage of Pneumonia was significantly lower among simple weaning than difficult weaning. Convulsions due to hypoxic ischemic insult one of most common causes of difficult weaning, anemia, heart failure, laryngeal edema have a rule in difficult weaning. Recommendations: Good monitoring of patients on MV and early management of any problem interferes with good ventilation.