The aim of this study was to investigate the trends and antimicrobial susceptibilities of methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates from outpatients and inpatients from April 2008 to March 2013 at Fukuoka University Chikushi Hospital. The proportion of MRSA among the S. aureus isolates from outpatients was stable over the study period, however, that from inpatients gradually decreased (p=0.026). There was no difference in the susceptibility to anti-MRSA agents between MRSA isolates from outpatients and inpatients, however, the susceptibilities to fosfomycin (FOM), minocycline (MINO), levofloxacin, erythromycin and clindamycin were higher in MRSA isolates from outpatients than from inpatients (48.6% vs. 35.6%, 56.1% vs. 40.1%, 38.2% vs. 4.9%, 16.2% vs. 3.9% and 18.5% vs. 4.5%, respectively, p<0.01). The susceptibility to FOM improved in MRSA from both outpatients and inpatients over time (p<0.05). In MRSA isolates from inpatients, the susceptibility to FOM and gentamicin increased significantly over the study period (p=0.023 and p=0.010, respectively), while, the susceptibility to MINO tended to decrease (p=0.094). The rate of MRSA isolates which were susceptible to more than two non-β-lactam antibiotics was significantly higher in outpatients than in inpatients (24.5% vs. 47.4%, p<0.01), however, this rate increased significantly during the study period only in inpatients, with a rate of 12.2% in 2008 and 53.1% in 2012 (p<0.01). In conclusion, our findings indicate a changing antimicrobial susceptibility of MRSA isolates, especially to non-β-lactam antibiotics. The determination of the prevalence and antimicrobial susceptibilities of MRSA clinical isolates will help physicians to select the initial empirical treatment.