Background & Objective: Ventilator-Associated Pneumonia (VAP) is the leading cause of death in Healthcare-Associated Infections (HCAI), with 30-day mortality of 59% of patients with ventilator devices. The aim of this research was to develop a VAP prevention model in the intensive care unit (ICU) based on Six Sigma and VAP Bundle, involving individual, organizational and work characteristics factors. Methodology: This research was carried out in the ICU, Poltekkes Kemenkes Malang, Malang, Indonesia, using a cross-sectional design. The research subjects were nurses, selected using a simple random sampling technique. All variables were measured through filling out questionnaires. Next, the measurement data was analyzed using Partial Least Square (PLS), based on Six Sigma and VAP Bundle. Results: Based on Six Sigma and VAP Bundle, the results of the analysis of the effects of the three factors on the implementation of VAP prevention were: 1) for individual factors, path coefficient = 0.189 and P = 0.000, so it was interpreted that this factor had a significant effect on the implementation of VAP prevention; 2) for organizational factors, path coefficient = 0.496 and P = 0.003, so it was interpreted that this factor also had a significant effect; 3) for the work characteristics factors, path coefficient = 0.289 and P = 0.000, so this factor also had a significant effect on the implementation of VAP prevention. Conclusion: Based on the research results, a VAP prevention model based on Six Sigma and VAP bundle was successfully built in the ICU, which involved organizational factors, work characteristics and individual factors. Abbreviations: HCAI - Healthcare-Associated Infections; HAP - Hospital-acquired pneumonia; PLS - Partial Least Square; SOP - standard operating procedure; VAP - ventilator-associated pneumonia; Keywords: Ventilator-Associated Pneumonia, VAP, Prevention; Six Sigma, VAP Bundle; Intensive Care Unit; organizational factors; work characteristics; individual factors Citation: Yuswanto TJA, Ernawati N, SolikhahFK, Nugroho HSW. Development of a prevention model for ventilator-associated pneumonia based on Six Sigma and VAP bundle. Anaesth. pain intensive care 2024;28(5):876−882; DOI: 10.35975/apic.v28i5.2574 Received: July 14, 2024; Reviewed: July 28, 2024; Accepted: July 28, 2024