Recently, a total of 74 Staphylococcus pseudintermedius isolates were collected from clinical cases of canine pyoderma and otitis externa in Korea. In this study, we examined in vitro fluoroquinolone resistance among those isolates using a standard disc diffusion technique. The results demonstrated that, except for one isolate, approximately 18.9% to 27.0% of the isolates possessed bacterial resistance to both veterinary- and human-licensed fluoroquinolones including moxifloxacin (18.9% resistance), levofloxacin (20.3% resistance), ofloxacin (24.3% resistance), ciprofloxacin (25.7% resistance), and enrofloxacin (27.0% resistance). Most surprisingly, 14 out of 74 (18.9%) isolates were resistant to all the five fluoroquinolones evaluated. Moreover, a PCR detection of the methicillin resistance gene (mecA) among the 74 isolates revealed that 13 out of 25 (52.0%) mecApositive isolates, but only 7 out of 49 (14.3%) mecA-negative isolates, were resistant to one or more fluoroquinones. Taken together, our results imply that bacterial resistance to both veterinary- and human-use fluoroquinolones becomes prevalent among the S. pseudintermedius isolates from canine pyoderma and otitis externa in Korea, as well as that the high prevalence of the mecA-positive S. pseudintermedius isolates carrying multiple fluoroquinolones resistance could be a potential public health problem.