ABSTRACT Aims and objectives To determine the effectiveness of an oral health care program for preventing ventilator‐associated pneumonia (VAP). Background Research has shown a significant correlation between oral bacteria and VAP, indicating that an oral health care program plays a very important role in VAP prevention. Design and methods A quasi‐experimental study was used and conducted in the intensive care unit in a medical centre. A total of 199 mechanically ventilated patients were enrolled and divided into two groups: the experimental group (n = 99) and control group (n = 100). The experimental group was cared for using an evidence‐based oral health care program, and the control group was cared for using routine nursing care procedures. Each group received the assigned treatment for four consecutive days. Results The incidence of VAP in the experimental group (4%, 4/95) was significantly lower than that in the control group (21%, 18/82). The oral assessment guide (OAG) mean score (9.16 ± 2·07) of the experimental group was significantly different (P < 0·05) from that of the control group (10·07 ± 1·79). The general estimated equation further showed that there was a significant difference between groups (P < 0·01) for the third post‐test data and no significant difference for the pre‐test or the first and second post‐test data between groups, indicating that an increased duration of intervention resulted in significant decreases in the OAG scores in the experimental group compared with the control group. Conclusions The evidence‐based oral health care program effectively improved oral mucosal health and statistically reduced the incidence of VAP in this study. Relevance to clinical practice The study findings may be useful as an empirical reference for health care professionals performing an oral health care program in the future. Additionally, it may serve as a reference for long‐term care policies aimed at reducing the ventilation duration, days of hospitalization and mortality rate to enhance patient safety and the quality of medical care.