We report results of a case-control study of the association between receipt of antimicrobial agents and diagnosis of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) in the United Kingdom. Eligible adults, selected from the General Practice Research Database, had no previous diagnosis of MRSA, no hospitalization in the past 2 years, and > or = 2 years of follow-up recorded in the database. For 2000-2004, we identified 1,981 MRSA case-patients and 19,779 matched control-patients. The odds ratios (ORs) and 95% confidence intervals (CIs) of MRSA diagnosis for patients who were prescribed 1, 2-3, or > or = 4 antimicrobial drugs were 1.57 (CI 1.36-1.80), 2.46 (CI 2.15-2.83), and 6.24 (CI 5.43-7.17), respectively. Risk for community-acquired MRSA increased with number of antimicrobial drug prescriptions, appeared to vary according to antimicrobial drug classes prescribed the previous year, and was highest for quinolones (OR 3.37, CI 2.80-4.09) and macrolides (OR 2.50, CI 2.14-2.91).