Ventilator-associated pneumonia is a common hospital-acquired infection. It causes patients to stay longer in the hospital and increases medical costs. This study explores the effect of applying an automatic medical information system to implement five-item prevention care bundles on the prevention of ventilator-related pneumonia. This study was a retrospective cohort study. This study was conducted from October 2017 to February 2018 and collected data from the intensive care unit of a medical center in southern Taiwan from January 2013 to May 2016. The control group (enrolled from January 2013 to June 2014) received oral hygiene. The experimental group (enrolled from July 2014 to December 2015) received five-item ventilator-associated pneumonia prevention care bundles, which consisted of (1) elevation of the head of the bed to 30–45°; (2) daily oral care with 0.12−0.2% chlorhexidine twice daily; (3) daily assessment of readiness to extubate; (4) daily sedative interruption; and (5) emptying water from the respirator tube. Results showed the incidence of ventilator-associated pneumonia in the bundle group was significantly less than the oral hygiene group (p = 0.029). The factors that significantly affected the incidence of ventilator-associated pneumonia were ventilator-associated pneumonia care bundle, ventilator-days, and intensive care unit length of stay. A significant reduction in ventilator-associated pneumonia rate in the bundle group compared to the oral hygiene group (OR = 0.366, 95% CI = 0.159–0.840) was observed, with 63.4% effectiveness. Application of an automatic medical information system to implement bundle care can significantly reduce the incidence of ventilator-associated pneumonia.