Background: Nebulization therapy is used for many therapies now including bronchodilators and corticosteroids and has a significant advantages superior to other routes of administration. However, it has many draw backs. Objective: To identify factors hindering the effect of nebulization therapy among critically ill mechanically ventilated patients. Settings: four intensive care units at Alexandria Main University. Subjects: A convenience sample of 60 adult critically patients on invasive MV and, all critical care nurses about 50 nurses who were involved in providing direct patient care and working in the three different shifts. Tool: “Factors hindering the effect of nebulization therapy among mechanically ventilated patients' assessment" was used to collect the needed data. Results: Findings of the current study revealed that there was a significant improvement in almost cardiovascular and respiratory parameters (p=<0.001* for all) after the nebulization therapy session with 4 hours, while Majority of the nurses had unsatisfactory level of performance regarding to nebulization therapy especially in the night shift with significant value for total score (p=0.006* for all). Conclusion: slower inspiratory flow, longer duty cycle, and large diameter tracheal tubes gives betters and effective nebulization. Recommendations: Frequent check of the ventilator parameters and connections before nebulization therapy, also providing frequent in- service training programs for the nurses related to the correct technique for nebulization therapy administration.