Background Methicillin-resistant Staphylococcus aureus (MRSA) infections are a concern across the worldwide. Methods Antibiotic stewardship and hand hygiene programs were reinforced in a 2,000-bed tertiary hospital in South Korea where the methicillin resistance rate of Staphylococcus aureus is about 65%. The computerized prescription restriction was implemented in August 2008. “Hand hygiene program,” consistent with World Health Organization guideline, was reinforced in December 2008. We assessed the effect of the infection control programs on the incidence of MRSA bloodstream infection (BSI) from January 2006 through November 2011. Results Incidence of MRSA BSI was reduced from 0.171 per 1,000 patient-days in 2009 to 0.116 per 1,000 patient-days in 2011 (P = .009). Monthly mean antibiotic consumption decreased from 690.54 ± 28.33 defined daily dose per 1,000 patients-days in 2008 to 652.47 ± 20.77 (P = .015) in 2011. The rates of performance in hand hygiene increased from 43% in 2008 to 83% in 2011 (P = .043). Conclusion Although we did not implement all components of “MRSA bundle,” efforts to reinforce antibiotic stewardship and hand hygiene program for 3 years had beneficial effects on the decrease in MRSA BSI in this institute with high rate of MRSA.