Several randomized controlled trials (RCTs) have examined the influence of oral chlorhexidine (CHX) in preventing nosocomial lower respiratory tract infection (LRTI). Most have failed to demonstrate a reduction in the incidence of LRTI. The present meta-analysis summarizes the effect of oral CHX on the development of LRTI. RCTs were identified through searching PubMed, MEDLINE and the Cochrane Central Register of Controlled Trials databases. Those describing the use of chlorhexidine for oral decontamination and reporting the incidence of LRTI as a study outcome were included in the meta-analysis. Seven RCTs met the inclusion criteria; pooling the results from these reveals a reduction in the relative risk (RR) of LRTI in the CHX group [RR(random): 0.58, 95% confidence interval (CI): 0.45-0.74; and RR(fixed): 0.56, CI95: 0.44-0.72, respectively]. Further analyses showed that this result applied only to patients ventilated for up to 48h (RR(random): 0.58, CI95: 0.45-0.74; and RR(fixed): 0.56, 95% CI: 0.44-0.72). Oral CHX should be included among preventive measures performed to reduce nosocomial LRTI. Whether it has an impact on the development of LRTI in patients requiring mechanical ventilation for a longer period of time remains unresolved.