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Supplemental Digital Content is Available in the Text. Background: Evidence suggests that the effect of 0.12% chlorhexidine (CHX) use for oral care on the development of ventilator-associated pneumonia (VAP) and ventilator-associated tracheobronchitis (VAT) is lacking. Evidence-based approaches to the prevention of VAP and VAT are of paramount importance for improving patients' outcomes. Objectives: This study aimed to (1) compare the effect of 0.12% CHX use for oral care on preventing VAP and VAT with the placebo group, as well as (2) compare its effect on oral health and prevention of oral microbial colonization with the placebo group. Methods: Prospective, single-blinded, randomized controlled trial performed in 2 intensive care units at a hospital. The sample comprised 57 mechanically ventilated adults randomly allocated to the 0.12% CHX group and the placebo group. Barnason's oral assessment guide was used to evaluate the oral health of both groups before oral care during the first 24 hr of tracheal intubation (Day 0) and at Day 2 and Day 3. Oropharyngeal secretion, endotracheal tube aspirate, and nonbronchoscopic bronchoalveolar lavage samples were collected on Day 0 and Day 3. Results: The rate of VAT development was not statistically different between the groups (p =.318). However, a significant difference existed in the rate of VAP development (p =.043). The frequency of oropharyngeal colonization significantly decreased in the 0.12% CHX group compared with the placebo group at Day 3 (p =.001). Conclusion: The use of 0.12% CHX for oral care could be effective for VAP prevention and reducing microbial colonization in mechanically ventilated patients. [ABSTRACT FROM AUTHOR]