This study assessed the susceptibility trend of methicillin-resistant Staphylococcus aureus (MRSA) in 5 Hong Kong hospitals from 1995 to 2005. Representative blood isolates were characterized to correlate the changes in resistance phenotypes with the clonal nature of MRSA. The prevalence of multisusceptible (MS) MRSA, defined by sensitivity to gentamicin, co-trimoxazole, and fusidic acid, was found to increase dramatically from <2% in 1995 to 1997 to 4.5% to 5.8% in 1998 to 1999 and remained at around 10% thereafter. Isolation of MS-MRSA was significantly associated with older age, convalescent care, and blood culture source. Molecular typing showed that the increasing isolation of MS-MRSA was associated with the spread of ST45/Staphylococcus cassette chromosome mec (SCCmec) IV or V with spa t1768, t1857, or t1081. Other features of the ST45 strains are as follows: agr4, capsular type 8, and Panton-Valentine leukocidin (PVL) negative. Two other epidemic clones, EMRSA-16 (ST36/SCCmec II) and CC398 (ST1277/SCCmec V), were detected as sporadic isolates for the first time in Hong Kong.