Introduction: Ventilator Associated Pneumonia (VAP) is a critical hospital acquired infection causing high morbidity and mortality among critically ill patients in intensive care units (ICU). Nurses play a fundamental role in prevention of VAP by adherence to evidence-based guidelines. Lack of knowledge and inadequate infection control program application are barriers against reduction of VAP incidence. Aim of work: To evaluate the effectiveness of an educational and training program of ICU nurses on their knowledge and practices regarding evidenced based guidelines for VAP prevention, to detect its impact on the incidence rate of VAP and to raise the nurses' awareness of their occupational health and safety by adherence to infection control guidelines. Materials and methods: A quasi- experimental pre-post design, interventional study was conducted on seventy nurses at five ICUs at the Manial hospital, Cairo University. Pre- intervention questionnaire and observational checklist were used to assess nurses' knowledge and practice of care bundle for VAP prevention. An educational and training programs about occupational health, safety and infection control measures was applied, and then post- intervention assessment was followed. Analysis of VAP incidence rate was performed after reviewing the medical records. Results: There was statistically significant improvement of knowledge in the post-intervention assessment except for the use of chlorhexidine which showed non-statistically significant differences between pre and post intervention (˃ 0.05). Nurses' practices regarding infection control measures and care bundle for VAP prevention showed statistically significant improvement in the post- intervention assessment (˂ 0.05) except for the use of clean unsterilized gloves and use of chlorhexidine swab which were the least practices adopted in 4.3% and 12.9% of nurses respectively. The mean VAP incidence rate was 24.86± 5.19 and was reduced to 5.47.96± in the post intervention phase (statistically significant). Conclusion: There was an overall improvement of nurses' knowledge and practices of evidence based guidelines for VAP prevention associated with reduction of VAP incidence rate after the implementation of the program.