BACKGROUND: Mechanically ventilated children are prone to pneumonia due to immobilization and lack of laryngeal (cough) reflex and swallowing. Nurses are directly responsible for many clinical approaches used to prevent ventilator-associated pneumonia. OBJECTIVE: The research objective is to determine the effectiveness of the nurse education program on the performance of nurses in providing oral care for mechanically ventilated children. METHODS: This quasi-experimental pretest-posttest design was conducted on 100 nurses (50 in each of the control and intervention groups) in pediatric intensive care units (PICU) in Tehran, 2015. The research tools included a demographic form and three checklists for evaluation of performance according to the clinical practice guidelines for the oral health status of children in PICU. Before intervention, the performance of nurses in both groups was observed at three stages and three different shifts, using an observational checklist. After one month, their performance was observed again with the same checklist at three stages and three different shifts in the PICU. The training was done in four 40-50 minute sessions in a workshop with a 4-week follow-up. The Chi-square test, Fisher’s exact test, paired t-test, independent t-test, and regression analysis comprised the tools used to analyze the data. FINDINGS: The mean performance scores of nurses before the education program in the intervention and control groups were 42.8 (+/-18.5) and 48.7 (+/-15.7), respectively. These scores improved to 68.6 (+/-31.4) and 48.6 (+/-15.4) four weeks after the intervention (p < 0.001). CONCLUSION: The performance of nurses in providing oral care for mechanically ventilated children improved after the intervention. It is recommended to implement this program for all nurses, regardless of their ward or specialty, based on the clinical practice guidelines. The periodic refreshing in-service training program should be provided to nurses in PICU in order to enhance their performance in providing oral care.