USA300 methicillin-resistantStaphylococcus aureus(MRSA) has been attracting worldwide attention as a cause of community-associated MRSA (CA-MRSA) infections in the 21st century. Nosocomial outbreaks of CA-MRSA clones have been progressively more reported in Europe and the USA, but only one very recent report from Kyoto found in Japan. In February 2008, a severe MRSA infection occurred in one immunocompromised patient and three healthy medical staff members at the Department of Dermatology, Graduate School of Medicine, University of the Ryukyus. The epidemiological and clinical pattern of the infection prompted us to characterize the molecular features of the MRSA strain involved. The causative MRSA strain belonged to the multi-locus sequence type 8, staphylococcal cassette chromosomemec(SCCmec) type IVa,spa1 (alternatively t008),agr1 and coagulase type III, and carried the Panton–Valentine leukocidin (PVL) gene and the arginine catabolic mobile element. Pulsed-field gel electrophoresis analysis showed that the MRSA responsible for the outbreak was the USA300 clone. All of the isolated USA300 clones had multiple resistance against six non-β-lactam antimicrobial drugs. We report here the first nosocomial outbreak of multidrug-resistant USA300 MRSA infections in Japan. This report shows that the USA300 clone can manifest severe skin infections such as furuncles and carbuncles even in healthy persons, which require drainage and i.v. treatment, and suggests that the clone can spread in hospital settings worldwide.