Background: Methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile are major nosocomial pathogens whose control relies on effective antimicrobial stewardship and infection control practices. This study evaluates the impact of a chlorine dioxidebased disinfectant (275 ppm) on the incidence of hospital-acquired (HA) MRSA and HA-Clostridium difficile infection (CDI) in a district general hospital. Methods: This study was carried out from November 2009 to September 2013. From November 2009 to October 2011 sodium dichloroisocyanurate was used for routine environmental disinfection. In November 2011, this was changed to a chlorine dioxide 275 ppm based disinfectant. This product was introduced into the hospital in a phased manner with intensive training on its use provided to all nursing, nursing auxiliary and hotel services staff. The effect of this change on the incidence of HA-MRSA and HA-CDI was assessed using segmented regression analysis of interrupted time series. In addition, the potential cost savings as a result of this intervention were assessed. Results: The HA-MRSA trend from November 2009 to October 2011 significantly increased (p=0.006). Following the introduction of the chlorine dioxide-based disinfectant there was significant decrease in the HAMRSA trend, with the monthly incidence being reduced by 0.003 cases/100 bed days (p=0.001), equating to an average of four cases per month after 12 months of use This resulted in an annual potential cost saving of £276 000. No significant effect on the incidence of HACDI was observed (coefficient -0.03; p=0.873). Conclusion This study highlights the importance of effective environmental inanimate surface decontamination in controlling the spread of MRSA and the potential cost savings that can be achieved through decreasing HA-MRSA rates.