Abstract Purpose This review aimed to determine the effectiveness of oral care using Chlorhexidine Gluconate(CHX) in Ventilator-Associated Pneumonia (VAP) in the intensive care unit. Methods An electronic databases search was conducted with Ovid-MEDLINE, EMBASE, CENTRAL, CINAHL and four domestic databases from July 10 to 16, 2018. Two reviewers independently selected the studies; three reviewers assessed their methodological quality and extracted relevant data. We conducted a metaanalysis of the effect of CHX oral care versus placebo using the Review Manager 5.3 software program and summarized the results of intervention from the included studies. Results Of the 512 articles identified, 17 randomized controlled trials met the inclusion criteria for review. The incidence of VAP differed significantly between the CHX and placebo groups(Relative Risk [RR]=0.72, 95% Confidence Interval [CI]=0.63~0.84). The pooled effects of oral care using 0.12% CHX were RR=0.65(95% CI=0.52~0.80) and RR=0.68 (95% CI=0.54~0.86) using CHX solution, which were statistically significant. When CHX oral care was performed three times a day, the size of the effect was statistically significant (RR=0.63, 95% CI=0.40~0.99). There was no significant difference in mortality between the CHX oral care and placebo groups (RR=1.08, 95% CI=0.94~1.28). Conclusion This review provides evidence that performing oral care using a 0.12% CHX solution three times a day could decrease the incidence of VAP. For improving the quality of nursing practice, the results of this review should be used as the basis for the oral care evidence-based practice guidelines for critical patients.