Hospitals in the northeast of Scotland have experienced methicillin-resistant Staphylococcus aureus (MRSA) outbreaks since 1997. Several infection control measures were introduced sequentially to control MRSA, and antibiotic use has been monitored. From January 1997 to December 2004, data on the monthly percentage of non-duplicate MRSA infections (%MRSA) were collated from an intervention hospital (IH) and a control hospital (CH). Both hospitals introduced the use of alcohol hand gel in November 2002. Furthermore, the IH introduced an environmental MRSA swabbing programme in March 2001, chlorine disinfection of the environment in September 2001, discharge screening in December 2001, admission screening in November 2003 and environmental audits in March 2004. Multivariate dynamic regression analysis was used to evaluate the longitudinal effects of these interventions as measured by new clinical cases of MRSA. At the IH, the %MRSA increased between January 1998 and January 2001 and then decreased. At the CH, the %MRSA increased from January 1997 to December 2004. Introduction of alcohol hand gel was associated with an absolute decrease in %MRSA of 21% and 30%, respectively, for the IH and CH. At the IH, introduction of chlorine disinfection and environmental swabbing were, respectively, associated with a decrease in %MRSA of 27% immediately and 32% 3 months later. Discharge screening and environmental audit did not significantly affect %MRSA, whereas admission screening was associated with a 22% decrease in %MRSA 4 months later. Increasing macrolide use was associated with increasing %MRSA in both hospitals, and increasing quinolone use was associated with increasing %MRSA in the CH. Implementation of stepwise infection control measures was associated with a decrease in %MRSA in the IH. Introduction of an alcohol gel for hand hygiene was associated with a decrease in %MRSA in both hospitals. Antibiotic use also affects %MRSA, in particular that of macrolides and quinolones.