Background: Patients on mechanical ventilation have a greater risk of acquiring infections; however, this problem is greatest in critical care units. Aim: Evaluate effect of educational program for nurses Performance regarding to infection control standard precautions, for patients on mechanical ventilation. Study design: Quasi-experimental research design was utilized in this study. Setting: The study was conducted in trauma ICU and emergency ICU at Assiut University hospital. Sample: A convenience sample of all available nurses. The sample size was 60 nurses. Tools: Utilizing two tools, Nurse's knowledge questionnaire and Observational checklist. Results: The majority of the studied Sample statistical significant difference between before and after educational program as regard to total nurses' knowledge and practice with P-value <0.001** .observed nurses' knowledge scores improved from 21.7% before the educational program to 75%after the educational program. In addition, the observed nurses' practice scores improved from 21.7%before the educational program to71.7%after educational program. Conclusion: Nurses` knowledge and practice regarding mechanical ventilation infection Control Standard Precautions in the trauma ICU and emergency ICU becomes to the satisfactory level after the educational program. Recommendation: Nurses need for continuous training programs to increase their performance regarding mechanical ventilation infection control standard Precautions.