Background: Ventilator-Associated Pneumoniais considered a severe health care-associated infection that results in severe morbidity and increase mortality rate. Moreover, it also lengthens hospital staying and increase hospital expenses. The study aims to evaluate the effect of care bundle strategies on nurses' performance regarding prevention of ventilator associated pneumonia at neonatal intensive care Units. Design: Quasi-experimental, pre- and post- intervention study. Subjects: All nurses(65) in neonatal intensive care units at 10th of Ramadan Charity Hospital and Aga Central Hospital. Tools: Two tools were used; 1st tool; sociodemographic data and predesigned questionnaire for nurses' knowledge and 2nd tool; observational checklist to assess nurses' performance regarding ventilator-associated pneumonia. Results: shows a significant improvement of nurses' knowledge regarding ventilator-associated pneumonia care bundle immediately after and at follow up in relation to neonates' positioning, oral care and ventilator care measures and the majority of them had a competent level of performance regarding observed ventilator-associated pneumonia care bundle before, immediately after and three months after program application. Conclusion: The application of care bundle strategies for the nurses had improved their level of knowledge and performance regarding prevention of ventilator-associated pneumonia with highly significant difference between mean score of total nurses' knowledge and performance. Recommendations: Continuous up to date guided protocols should focus on enhancing nurses' performance regarding ventilator-associated pneumonia care bundle.