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Background: Preventing Ventilator-Associated Pneumonia (VAP) is an important strategy to increase the quality of provided care for patients under mechanical ventilation. Rose water is the main product of Rosa damascena which is a popular medicinal plant and has been widely used in alternative medicine. It has antibacterial activity against gram-negative and gram-positive bacteria which can potentially cause VAP. Materials and Methods: This study was a randomized, controlled, single-center trial. 88 patients in a 21-bed surgical Intensive Care Unit (ICU) who were under mechanical ventilation met the inclusion criteria, and 80 patients fulfilled the study. Based on receiving either rose water and chlorhexidine solution or chlorhexidine solution alone, the patients were divided into two groups of control and intervention. The incidence of VAP up to 14 days was the primary outcome. Duration of mechanical ventilation, the ICU length of stay, and mortality in ICU were the secondary outcomes. Results: There was no significant difference in demographic data, the incidence of VAP, the incidence of late-onset VAP, mechanical ventilation days, length of the ICU stay, and mortality between the two groups. However, the incidence of early-onset VAP in the intervention group was significantly lower than in the control group (p= 0.021). Conclusion: Rose water mouthwash significantly reduced the risk of earlyonset VAP without any effect on late-onset VAP. [ABSTRACT FROM AUTHOR]