Staphylococcus aureus, including methicillin-sensitive and-resistant S.aureus (MSSA and MRSA), are associated with severe nosocomial human infections.This study aimed to investigate the molecular profile, including its dynamic changes and genotype-phenotype correlation of S.aureus isolates recovered from different clinical specimens of inpatients with S.aureus infection over a six-year span at a teaching hospital in Shanghai, China.Between 2005 and 2010, random sample of 610 unique S.aureus isolates were collected from different clinical samples of inpatients with S.aureus infection for molecular and antibiotic susceptibility analysis.Our results showed that among the 610 S.aureus isolates, 20 MLST sequence types (STs; primarily ST239, ST5, ST7, ST188, and ST398) and 52 spa types (primarily t002, t037, t030, and t601) were found.These isolates belonged to 14 clonal complexes (CCs; primarily CC8, CC5,CC7, and CC188).In total, 444 isolates (72.8%) were MRSA and 166 (27.2%) were MSSA.The ST239-MRSA-Ⅲ-spa t037 and ST5-MRSA-Ⅱ-spa t002 were the most predominant MRSA clones.From 2005 to 2010, spa t002, spa t037, and their corresponding STs (ST5 and ST239) were the most frequent clones among all of the S.aureus isolates and showed the most resistant phenotypes to various antibiotics.Generally, the different genotypes showed different drug resistance rates, but no isolates were resistant to vancomycin, teicoplanin, or linezolid.The profiles of virulence and resistance genes differed by genetic background, with the ST239, ST5, spa t030, spa t037, spa t002, and spa t601 strains showing higher resistance rates to gentamicin, cefoxitin, ampicillin, cefazolin, erythromycin, clindamycin and levofloxacin than strains of other types.Moreover, the antiseptic resistance genes qacA/B were generally associated with these six types.The prevalence of STs were different among different clinical specimens, which also changed by year.Recently(2009 to 2010), the distribution of predominant types decreased, while the prevalence of non-predominant STs, most of which belonged to MSSA, increased, especially for the isolates from blood and other fluids.Continual monitoring of clinical isolates is necessary to develop and maintain an effective strategy against S.aureus infection in the hospital setting.