Introduction: Daptomycin, a novel lipopeptide antibiotic, has been introduced recently to clinical use in our country. It is approved for the treatment of complicated skin and soft tissue infections caused by gram-positive microorganisms, Staphylococcus aureus bacteremia, and right-sided endocarditis due to methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA). Its interaction with other therapeutic agents is not well studied. Although there are several studies about the combination of daptomycin with other groups of antibiotics, particularly with beta-lactams, to the best of our knowledge, there has been no study regarding daptomycin and quinolones combination therapy. In this respect, the interactions between daptomycin and quinolones (levofloxacin, ciprofloxacin) were studied in vitro. Materials and Methods: The study was held in Gazi University School of Medicine, Infectious Diseases and Clinic Microbiology Laboratory, between July 2006 and December 2009. In vitro susceptibilities and synergistic activities of daptomycin, levofloxacin and ciprofloxacin were investigated using E-test method in 20 MSSA and 20 MRSA consecutive isolates, which were identified as a cause of nosocomial bloodstream infection. Results: Only one isolate from each patient was included in the study. Fractional inhibitory concentration (FIC) index values were calculated and classified as synergistic (FIC 4). All isolates were susceptible to daptomycin. Although there was no resistance to levofloxacin and ciprofloxacin in MSSA strains, 85% resistance was determined in MRSA strains to both antibiotics. According to FIC index values, neither synergistic nor antagonistic activity between daptomycin-levofloxacin or daptomycin-ciprofloxacin was observed. Conclusion: Although there is no synergistic activity between daptomycin and quinolones against S. aureus isolates, no antagonistic activity was detected either. Even though there are no data about the clinical use of these combinations, it is thought that these drugs can be used in combination for the treatment of selected cases