Background: Mechanical Ventilation is widely used in the Intensive Care Units worldwide for various emergency indications. So, nurses must be knowledgeable about the function and limitations of ventilator modes, causes of respiratory distress and dys-synchrony with the ventilator and appropriate management in order to provide high-quality patient-centered care. Aim: was to assess nurses' performance regarding management of patients on mechanical ventilator.Subject and Methods: Setting:the study was conducted in the Intensive Care Units (ICUs) at Mansura University Emergency Hospital. Design was descriptive design and including 60 nurses. Tools: Two tools were used for data collections: tool I: interview questionnaire sheet to assess nurses' demographic characteristics and nurses' information regarding management of patient on mechanical ventilator. Tool II: observational checklist for their practice. Results: showed that , 68.3% of nurses had unsatisfactory knowledge; all nurses in the study (100%) had unsatisfactory practice regarding the management of patients on the mechanical ventilation ;there was statistically significant relation between nurses' practice regarding the management of patients on the mechanical ventilator and their demographic characteristics in area of occupation and no correlation between nurses' knowledge and practice regarding the management of patients on the ventilator. Conclusion: Based on the study finding, the majority of nurses caring for the patients on mechanical ventilator had unsatisfactory knowledge and practice.Recommendtion:  Recommended that the nurses should be trained enough to give effective and safe care to such patients.