Purpose. The aim of this review was to evaluate the evidence on the effectiveness of oral chlorhexidine in the prevention of ventilator-associated pneumonia (VAP) in critically ill adult mechanically ventilated patients in intensive care units (ICUs). Methodology. An extensive literature search of studies published in English was undertaken between June 2010 and June 2011. Electronic databases searched were the Cochrane Central Register of Controlled Trials (CENTRAL), the Cumulative Index of Nursing and Allied Health (CINAHL) and MEDLINE. Reference lists of articles, textbooks and conference summaries were examined and hand searching was performed. Literature searches were done using the following Medical Subject Headings (MeSH) terms: ventilator-associated pneumonia, VAP, chlorhexidine, hospital-acquired pneumonia, nosocomial infections, mechanically ventilated patients, intensive care, mouthwash, mouth care, oral care, oral hygiene and dental care. Selection criteria. Two reviewers selected the studies independently. Eight randomised controlled trials investigating the efficacy of oral chlorhexidine versus power tooth brushing, Listerine, placebos, bicarbonate isotonic serum rinse and normal saline in the prevention of VAP in adult mechanically ventilated, critically ill patients in ICUs met the inclusion criteria. Data collection and analysis. All relevant data were entered into Review Manager (version 5.1) for analyses. The effect measure of choice was the risk ratio (RR) with 95% confidence intervals (CIs) for dichotomous data using the random effects (Mantel-Haenszel) model (p-value 0.05). Heterogeneity was assessed using the Cochrane Q statistic and I². Results. Eight randomised controlled trials met the inclusion criteria for this review. There was a 36% higher chance of VAP in the control group compared with the chlorexidine group (RR 0.64, 95% CI 0.44 - 0.91). The variation between the included studies was very small (χ²=0.24). Conclusion. Treatment with chlorhexidine decreased the risk of VAP by 36%. The use of 2% chlorhexidine may be most effective in reducing the incidence of VAP. There was no evidence of an effect of chlorhexidine on mortality.