Background: Several studies showed that the implementation of the Institute for Healthcare Improvement (IHI) ventilator bundle alone or with other preventive measures are associated with reducing Ventilator-Associated Pneumonia (VAP) rates. However, the association with ventilator utilization was rarely examined and the findings were conflicting. The objectives were to validate the bundle association with VAP rate in a traditionally high VAP environment and to examine its association with ventilator utilization. Materials and Methods: The study was conducted at the adult medical-surgical intensive care unit (ICU) at King Abdulaziz Medical City, Saudi Arabia, between 2010 and 2013. VAP data were collected by a prospective targeted surveillance as per Centers for Disease Control and Prevention (CDC)/National Healthcare Safety Network (NHSN) methodology while bundle data were collected by a cross-sectional design as per IHI methodology. Results: Ventilator bundle compliance significantly increased from 90% in 2010 to 97% in 2013 (P for trend < 0.001). On the other hand, VAP rate decreased from 3.6 (per 1000 ventilator days) in 2010 to 1.0 in 2013 (P for trend = 0.054) and ventilator utilization ratio decreased from 0.73 in 2010 to 0.59 in 2013 (P for trend < 0.001). There were negative significant correlations between the trends of ventilator bundle compliance and VAP rate (cross-correlation coefficients −0.63 to 0.07) and ventilator utilization (cross-correlation coefficients −0.18 to −0.63). Conclusion: More than 70% improvement of VAP rates and approximately 20% improvement of ventilator utilization were observed during IHI ventilator bundle implementation among adult critical patients in a tertiary care center in Saudi Arabia. Replicating the current finding in multicenter randomized trials is required before establishing any causal link.