BACKGROUND: The purpose of this study was to determine the efficacy of infection-control interventions to decrease the incidence of catheter-associated bloodstream infections (CA-BSI) and to examine the sustainability of its effect during and after the intervention in Korea. MATERIALS AND METHODS: We conducted a prospective multi-strategy intervention in intensive care units (ICUs) at 3 university hospitals in Korea. The intervention consisted of education and on-site training for medical personnel involved in catheter care, active surveillance, and reinforcement of current intervention in each unit. After the intervention of 3 months, we identified CA-BSI cases of each hospital using the electronic database for 6 months. RESULTS: During the intervention, the number of CA-BSI decreased significantly compared to pre-interventional period (8.7 vs. 2.3 per 1,000 catheter days; rate ratio 0.28; 95% CI, 0.13-0.61). After the intervention, CA-BSI rate increased slightly, but was still significantly lower than that of pre-interventional period (4.3 per 1,000 catheter days; rate ratio, 0.49; 95% CI, 0.31-0.78). Reduction of gram-negative bacterial infections was noted during and after the intervention. CONCLUSIONS: A multi-strategy approach to reduce CA-BSI could be implemented in diverse settings of medical and surgical units in Korea and decreased CA-BSI rates during the intervention.