Since 2002, we have conducted a series of intervention programs in Sado Island, Japan, to increase awareness of the appropriate use of antimicrobials among public and health-care staff. The objective of our study was to determine the antimicrobial susceptibility of Staphylococcus aureus among children in a semi-closed geographic region with controlled antimicrobial use. The average hospital visit-based rate for antimicrobial drug prescription drastically decreased from 535 per 1,000 clinic visits before the intervention programs to 45-75 per 1,000 clinic visits after the intervention programs (P < 0.0001). We obtained 1,260 clinical isolates of S. aureus from 957 pediatric outpatients aged 0-15 years between 2002 and 2010 at Sado General Hospital. The prevalence of methicillin-resistant S. aureus (MRSA) in the final year of the study (2010, 7.9%) was significantly lower than that in the early period of the study (2003, 23.6%; P < 0.001). All tested S. aureus isolates were susceptible to trimethoprim/sulfamethoxazole, teicoplanin, linezolid, and vancomycin. The prevalence of gentamicin-resistant S. aureus in isolates from skin lesions was significantly higher than in isolates from other lesions (41.3% versus 28.5%; P < 0.05). In conclusion, prevalence of MRSA in children in our study population could be decreased by eliminating unnecessary antimicrobial drug prescriptions.