Abstract Introduction Methicillin-resistant Staphylococcus aureus (MRSA) is a leading pathogen of healthcare-associated infections in intensive care units (ICUs). Prior studies have shown that decolonization of MRSA carriers is an effective method to reduce MRSA infections in ICU patients. However, there is currently a lack of data on its effect on mortality and medical cost. Methods Using a quasi-experimental, interrupted time-series design with re-introduction of intervention, we evaluated the impact of active screening and decolonization on MRSA infections, mortality and medical costs in the surgical ICU of a university hospital in Taiwan. Regression models were used to adjust for effects of confounding variables. Results MRSA infection rate decreased from 3.58 (baseline) to 0.42‰ (intervention period) (P