Staphylococcus epidermidis is a harmless commensal, but it can become a human pathogen, mainly in the hospital environment. In order to clarify strategies used by these bacteria to adapt to the hospital environment, we compared the population structure and staphylococcal cassette chromosome mec (SCCmec) content of S. epidermidis from the community and hospital. S. epidermidis were collected from nasal swabs of both healthy military draftees (192 isolates) and patients (94 isolates) recovered in the same time period and geographical region. S. epidermidis were characterized by PFGE, multilocus sequence typing and SCCmec typing. Clonal complex 5 was predominant in the hospital (100) and the community (58), but some clonal types were specific to each environment and others were found in both (C/H clones). The methicillin-resistant S. epidermidis (MRSE) colonization rate in the community was very low (7) when compared with the hospital (30; P0.05). Community-associated MRSE carried mostly SCCmec IV and V [Simpsons index of diversity (SID)57.52; 95 CI 38.3576.69], whereas hospital-associated MRSE carried 17 SCCmec structures (SID82.67; 95 CI 77.3887.96). Isolates of the same PFGE type had a much higher number of different SCCmec types when collected in the hospital than in the community. Our data suggest that the S. epidermidis population is composed of hospital-associated clonal types, community-associated clonal types and types that are able to survive in both environments. Moreover, adaptation to the hospital environment in S. epidermidis appears to promote an increase in the frequency and diversification of SCCmec.