Background: Mechanical ventilation is one of the most significant life-saving advancements in medical science; Nurses caring for patients on ventilator must be competent to provide effective nursing care for such group of patients, Effective educational program for nurse's staff will increase the quality of nursing care. Aim: To investigate the effect of educational program on nurses' knowledge and practice caring for patients on mechanical ventilation. Study design: Quasi-experimental research design was utilized in this study. Setting: The study was conducted in trauma ICU at Assiut University hospital. Sample: A convenience sample of all available nurses. The sample size was (50) nurse. Tools: Two tools were used for data collection, Tool one: nurses' knowledge assessment tool, Tool two Nurses practice assessment tool. Results: Nurses' knowledge scores improved after implementation of the educational program from (44% to 84%), Also the observed nurses' practice scores improved from (38%) before the educational program to (90%) after the educational program. Conclusion: Nurses` knowledge and practice regarding the care of patients on ventilator in the trauma intensive care unit becomes to the satisfactory level after the educational program. Recommendation: Nurses need for in-service training programs to update their knowledge and practice regarding the care of patients on ventilator.