Objective: Review the literature to identify the most effective method of oral hygiene to reduce the incidence of ventilator-associated pneumonia (VAP). Background: Ventilator-associated pneumonia is the most common nosocomial infection in patients being treated with mechanical ventilation. Method: This study is a systematic literature review. The databases searched included Web of Science, Cumulative Index to Nursing and Allied Health Literature, Ovid, and MEDLINE. Results: Implementation of oral care protocols and nurse education programs reduced VAP. Although chlorhexidine was the most popular oral care product, no consensus emerged on concentration or protocols for oral care. Conclusion: No consensus on best practice for oral hygiene in patients being treated with mechanical ventilation was found. Chlorhexidine was the most popular oral care product. Implementation of an oral care protocol, ongoing nurse education, and evaluation were important in reducing the incidence of VAP. Future research should analyze chlorhexidine concentration, application techniques, and frequency of oral care, to optimize VAP prevention.