Implementation of standardised oral hygiene protocols could potentially minimise the occurrence of ventilator-associated pneumonia (VAP) among critically ill patients. However, inclusion of the topical application of oral chlorhexidine as an effective oral antiseptic in such protocols and VAP guidelines remains controversial and questionable, due to inconstancy in the current evidential findings. The aim is to investigate the efficacy of oral chlorhexidine in reducing the incidence of VAP among mechanically ventilated patients in different critical care settings. A comprehensive electronic and manual literature search was conducted utilising different databases, including Cinahl, Medline, PubMed, Google Scholar and Scopus, and using related keywords to identify the relevant primary research sources published in English since 2005. Data were extracted and summarised in tables and then were critically appraised using validated tools. When the relevant studies were analysed, they were grouped based on two main themes and varied subthemes. One of these is the patient population, including those admitted to mixed or general ICU and those who had undergone cardiac surgery. The second theme is the chlorhexidine type, in which solution and gel were investigated at varied concentration using different frequencies. Topical application of chlorhexidine may have the potential benefit of reducing VAP incidence; however, no recommendation can be made regarding the best type or optimal concentration that can be used. Thus, a large-scale randomised control trial to investigate further the effectiveness of its routine use among mixed ICU patients and to demonstrate the optimal form, as well as concentration and frequency, is required