Background. We sought to determine the long-term effect of a multifaceted infection-control intervention to reduce the incidence of pandrug-resistant Acinetobacter baumannii infection in a Thai tertiary care center. Methods. A 3-year, prospective, controlled, quasi-experimental study was conducted in medical intensive care, surgical intensive care, and coronary care units for a 1-year period before intervention (period 1), a 1-year period after intervention (period 2), and a 1-year follow-up period (period 3). The interventions in period 2 included strictly implementing contact isolation precautions and appropriate hand hygiene, active surveillance, cohorting patients who were colonized or infected with pandrug-resistant A. baumannii, and environmental cleaning with 1:100 sodium hypochlorite solution. All interventions were continued in period 3, but environmental cleaning solutions were changed to detergent and phenolic agents. Results. Before the intervention, the rate of pandrug-resistant A. baumannii colonization and/or infection was 3.6 cases per 1000 patient-days. After the intervention, the rate of pandrug-resistant A. baumannii colonization and/or infection decreased by 66% in period 2 (to 1.2 cases per 1000 patient-days; P < .001) and by 76% in period 3 (to 0.85 cases per 1000 patient-days; P < .001). The monthly hospital antibiotic cost of treating pandrug-resistant A. baumannii colonization and/or infection and the hospitalization cost for each patient in the intervention units were also reduced by 36%-42% (P < .001) and 25%-36% (P < .001), respectively, during periods 2 and 3. Conclusions. A multifaceted intervention featuring active surveillance and environmental cleaning resulted in sustained reductions in the rate of pandrug-resistant A. baumannii colonization and infection, the cost of antibiotic therapy, and the cost of hospitalization among intensive care unit patients in a developing country.