Similar to many hospitals worldwide, Aberdeen Royal Infirmary has had an outbreak of methicillin-resistant Staphylococcus aureus (MRSA). In this setting, the outbreak is attributable to two major clones. The relationships between antimicrobial use and MRSA prevalence were analyzed by time-series analysis. From June 1997 to December 2000, dynamic, temporal relationships were found between monthly %MRSA and previous %MRSA, macrolide use, third-generation cephalosporin use, and fluoroquinolone use. This study suggests that use of antimicrobial drugs to which the MRSA outbreak strains are resistant may be an important factor in perpetuating the outbreak. Moreover, this study confirmed the ecologic effect of antimicrobial drug use (i.e., current antimicrobial use) may have an effect on resistance in future patients. Although these results may not be generalized to other hospitals, they suggest new directions for control of MRSA, which has thus far proved difficult and expensive.