BACKGROUND: Ventilator-associated pneumonia (VAP) is common in critical patients and related with increased morbidity and mortality. We conducted a systematic review and meta-analysis, with intention-to-treat analysis, of randomized controlled clinical trials that assessed the effectiveness of different intraoral chlorhexidine protocols for the prevention of VAP. METHODS: Search strategies were developed for the MEDLINE, EMBASE, and LILACS databases. MeSH terms were combined with Boolean operators and used to search the databases. Eligible studies were randomized controlled trials of mechanically ventilated subjects receiving oral care with chlorhexidine or standard oral care protocols consisting of or associated with the use of a placebo or no chemicals. Pooled estimates of the relative risk and corresponding 95% CIs were calculated with random effects models, and heterogeneity was assessed with the Cochran Q statistic and I 2 . RESULTS: The 13 included studies provided data on 1,640 subjects that were randomly allocated to chlorhexidine (n ‫؍‬ 834) or control (n ‫؍‬ 806) treatments. A preliminary analysis revealed that oral application of chlorhexidine fails to promote a significant reduction in VAP incidence (relative risk 0.80, 95% CI 0.59 -1.07, I2 ‫؍‬ 45%). However, subgroup analyses showed that chlorhexidine prevents VAP development when used at 2% concentration (relative risk 0.53, 95% CI 0.31-0.91, I 2 ‫؍‬ 0%) or 4 times/d (relative risk 0.56, 95% CI 0.38 -0.81, I2 ‫؍‬ 0%). CONCLUSIONS: We found that oral care with chlorhexidine is effective in reducing VAP incidence in the adult population if administered at 2% concentration or 4 times/d.