Background. Ventilator-associated pneumonia (VAP) is considered to be an important cause of infection-related death and morbidity in intensive care units (ICUs). We sought to determine the long-term effect of an educational program to prevent VAP in a medical ICU (MICU). Methods. A 4-year controlled, prospective, quasi-experimental study was conducted in an MICU, surgical ICU (SICU), and coronary care unit (CCU) for 1 year before the intervention (period 1), 1 year after the intervention (period 2), and 2 follow-up years (period 3). The SICU and CCU served as control ICUs. The educational program involved respiratory therapists and nurses and included a self-study module with preintervention and postintervention assessments, lectures, fact sheets, and posters. Results. Before the intervention, there were 45 episodes of VAP (20.6 cases per 1000 ventilator-days) in the MICU, 11 (5.4 cases per 1000 ventilator-days) in the SICU, and 9 (4.4 cases per 1000 ventilator-days) in the CCU. After the intervention, the rate of VAP in the MICU decreased by 59% (to 8.5 cases per 1000 ventilator-days; P = .001) and remained stable in the SICU (5.6 cases per 1000 ventilator-days; P = .22) and CCU (4.8 cases per 1000 ventilator-days; P = .48). The rate of VAP in the MICU continued to decrease in period 3 (to 4.2 cases per 1000 ventilator-days; P = .07), and rates in the SICU and CCU remained unchanged. Compared with period 1, the mean duration of hospital stay in the MICU was reduced by 8.5 days in period 2 (P < .001) and by 8.9 days in period 3 (P < .001). The monthly hospital antibiotic costs of VAP treatment and the hospitalization cost for each patient in the MICU in periods 2 and 3 were also reduced by 45%-50% (P < .001) and 37%-45% (P < .001), respectively. Conclusions. A focused education intervention resulted in sustained reductions in the incidence of VAP, duration of hospital stay, cost of antibiotic therapy, and cost of hospitalization.