Background: In critically ill patients undergoing mechanical ventilation, aerosol inhalation is a common intervention. An international survey demonstrated that 99% of 611 ICUs from 70 countries reported using aerosol therapy during mechanical ventilation. Many factors may affect the efficacious delivery of aerosols to the lungs. These factors are associated with patients, drugs, devices, artificial airways, ventilator settings, ventilator circuits and nurse’s practice. The study was aimed to assess factors affecting nebulization therapy for patients with mechanical ventilation in emergency care units. Setting: The present study was conducted in two surgical intensive care units at surgical hospital at Zagazig university hospitals, Egypt. Study subjects a convenient sample of available emergency care nurses (30) working in the mentioned setting and a purposive sample of (30) patients who fulfilling the inclusion criteria. Tool of data collection: Three tools were used for collecting data. Tool I: An interview questionnaire to assess factors affecting nebulization therapy for patients with mechanical ventilation. Tool II: Self-administered questionnaire for nurses. Tool III: Observational checklist to assess nurse’s practice regarding nebulization therapy administration. Results: There was statistically significant difference in pulse Immediately after session and 4 hrs after session; Also there was highly statistically significant difference in Systolic blood pressure, Diastolic blood pressure before, immediately after and 4 hrs after session at (p ≤ 0.01)., Majority of studied nurses (80.0%) of the studied nurses had unsatisfactory level of total knowledge, (86.7%) of the studied nurses had inadequate practice regarding nebulization therapy administration. Conclusion: Nebulized bronchodilators and corticosteroids can increase blood pressure, improve oxygen saturation, decrease (plateau pressure, peak inspiratory pressure) and increase static compliance, majority of studied nurses had unsatisfactory knowledge and inadequate practice. Recommendation: It is highly recommended to create training opportunities for nurses to increase their knowledge about nebulizer devices. In addition, we should establish a team of professionals to regularly measure nurses' knowledge of inhaler devices and Regular assessment and ongoing education on the correct inhaler technique for respiratory nurses are necessary to optimize device usage by nurses. Finally, related institutional improvements are important. Keywords: Factors, Nebulization, Therapy, Mechanical ventilation, Emergency, Care unit.