PURPOSE: This study developed and evaluated a systematic intervention among medical ICU nurses for preventing ventilator-associated pneumonia (hereafter VAP). METHODS: A VAP prevention program was proposed based on a literature review, revised to fit the target situation, and validated. It was composed of one-time interventions including education, pamphlets, hand cultures, and a quiz event, as well as repeated interventions such as posters, reminders, posting hand culture results, and performance feedback. A simulated control group pretest-posttest design was used to verify the effectiveness of the VAP control program. The incidence of VAP among ICU patients was measured both during 3 months before (n = 80) and during 3 months after (n = 75) intervention. RESULTS: The VAP prevention program's effectiveness, with a pre-intervention VAP rate of 17.38 and post-intervention rate of 11.04 per 1,000 ventilator days, showed a clinical tendency to decrease, but the difference was not statistically significant (p = .750). CONCLUSION: A VAP prevention program of multiple interventions can be useful in decreasing the VAP rate. Given that the monthly decrease in the VAP rate was not considered statistically significant, long-term research needs to be done. Additionally, since this study targeted only nurses, it is suggested that future research targets other health care workers who can influence VAP rates.