Background:The relationship between the oral care and ventilator-associated pneumonia (VAP) was confirmed in patients undergoing ventilation. Objectives: The current study aimed at investigating the effects of chlorhexidine gluconate (CHX) and ozonated water on the prevention of VAP. Methods: The current double-blind, randomized, clinical trial with the experimental and control groups was conducted in Iran in 2014. In the current study, 75 inpatients undergoing ventilation were grouped through the convenience sampling method and randomly allocated into 2 groups based on the inclusion criteria. In the experimental group (39 patients), oral care provided by ozonated water, while in the control group (35 patients), oral care was provided via CHX. Clinical pulmonary infection score (CPIS) was used to examine the rate of VAP infection. Results: According to the results of the current study, the occurrence rate of VAP in the experimental and control groups were 2.4% and 8.3%, respectively that was equal until the 3rd day (P value = 0.339). However, on the 4th day, the VAP occurrence rate in the experimental group (14.6%) was significantly lower than that of the control group (30.6%) (P value = 0.02). Conclusions: Based on the results, ozonated water was more effective to prevent VAP than CHX. Ozone water can be used as a suitable alternative mouthwash in patients undergoing mechanical ventilation.