Fifty methicillin and multi-resistant Staphylococcus haemolyticus (MRSH) strains, were tested against daptomycin and comparators. Daptomycin showed an overall MIC(90) value of 1 mg/L, similar to that of quinopristin/dalfopristin and lower than the values for vancomycin (2 mg/L), linezolid (2 mg/L) and teicoplanin (32 mg/L). Eighteen strains showed heteroresistant subpopulations with teicoplanin, whereas two strains were also heteroresistant to vancomycin and these sub-populations retained susceptibility to daptomycin. Our results show the good in vitro activity of daptomycin in MRSH strains possessing a multi-resistant phenotype. Clinical data on daptomycin efficacy are necessary to confirm our in vitro findings.