We carried out a systematic review and meta-analysis of randomized trials to explore the effectiveness of oral chlorhexidine on nosocomial pneumonia, causative bacteria, and mortality. PubMed, Embase, and the Cochrane Register of Controlled Trials were searched for randomized trials in critically ill patients receiving oral chlorhexidine. Odds ratios (OR) were pooled with the random effects model. Twenty-two randomized trials including 4277 patients were identified. Chlorhexidine significantly reduced the incidence of nosocomial pneumonia (OR 0.66; 95% confidence interval [CI] 0.51-0.85) and ventilator-associated pneumonia (OR 0.68, 95% CI 0.53-0.87). There was a significant reduction of nosocomial pneumonia due to both Gram-positive (OR 0.41; 95% CI 0.19-0.85) and Gram-negative (OR 0.68; 95% CI 0.51-0.90) bacteria, but only pneumonia due to "normal" flora (OR 0.51; 95% CI 0.33-0.80). The subgroup analysis revealed a significant benefit of chlorhexidine on nosocomial pneumonia in surgical patients only (OR 0.52; 95% CI 0.33-0.82). Mortality was not affected. This review indicates that in critically ill, mainly surgical, patients, oral chlorhexidine reduces nosocomial pneumonia, ventilator-associated pneumonia, nosocomial pneumonia due to Gram-positive and Gram-negative bacteria, and due to "normal" flora, without affecting mortality. Further studies should explore the efficacy of oral chlorhexidine in non-surgical critically ill population.