Background: Staphylococcus aureus is the most common pathogen responsible for skin and soft tissue infections worldwide. Methicillin-resistant S. aureus is a major cause of both nosocomial and community acquired infections. The emergence of antimicrobial-resistant S. aureus is of global concern. Fluoroquinolone antimicrobials including ciprofloxacin, levofloxacin, and moxifloxacin are used to treat skin and soft tissue infections due to S. aureus. Emergence of ciprofloxacin resistance has increased in community acquired methicillin-resistant S. aureus strains. The aim of this study was to evaluate the minimum inhibitory concentration of ciprofloxacin and hexahydroquino-line derivatives against methicillin- and ciprofloxacin-resistant S. aureus.Methods: Identification of S. aureus was performed by routine microbiological tests in the Department of Pathobiology in Winter 2012. The susceptibility of S. aureus strains to both methicillin and ciprofloxacin was examined by the Kirby-Bauer disk-diffusion method. The minimum inhibitory concentration of ciprofloxacin, hexahydroquinoline derivatives and their combination were separately determined by broth microdilution method against methicillin- and ciprofloxacin-resistant S. aureus.Results: The minimum inhibitory concentration of ciprofloxacin decreased in the presence of hexahydroquinolinein derivatives in comparison with ciprofloxacin alone.Conclusion: This study showed that hexahydroquinoline derivatives enhance the antibacterial effect of ciprofloxacin against methicillin- and ciprofloxacin-resistant S. aureus. Therefore, these derivatives could be used as inhibitors of antibiotic resistance in combination therapies. This enhancement may be related to the inhibitory effect of hexahydroquinoline derivatives on the expression of antibiotic efflux pump in the bacteria. However, the structural features of a fluoroquinolone that determine whether it is affected by efflux transporters are not fully defined.