Background. We conducted a study to evaluate the impact of education and an antibiotic-control program on antibiotic-prescribing practices, antibiotic consumption, antimicrobial resistance, and cost of antibiotics in a tertiary care hospital in Thailand. Methods. A study of the year before and the year after the intervention was performed. Inpatient antibiotic prescriptions were prospectively observed. Demographic characteristics, hospital unit, indication for antibiotic prescription, appropriateness of antibiotic use, reasons for inappropriate antibiotic use, antibiotic consumption (i.e., the rate of antibiotic use), bacterial resistance, and antibiotic cost data were collected. Interventions included education, introduction of an antibiogram, use of antibiotic prescription forms, and prescribing controls. Results. After the intervention, there was a 24% reduction in the rate of antibiotic prescription (640 vs. 400 prescriptions/1000 admissions; P < .001). The incidence of inappropriate antibiotic use was significantly reduced (42% vs. 20%; P < .001). A sustained reduction in antibiotic use was observed (R2 = 0.692; P<.001). Rates of use of third-generation cephalosporins (31 vs. 18 defined daily doses [DDDs]/1000 patient-days; P < .001) and glycopeptides (3.2 vs. 2.4 DDDs/1000 patient-days; P = .002) were significantly reduced. Rates of use of cefazolin (3.5 vs. 8.2 DDDs/1000 patient-days; P < .001) and fluoroquinolones (0.68 vs. 1.15 DDDs/1000 patient-days; P < .001) increased. There were no significant changes for other antibiotic classes. Significant reductions in the incidence of infections due to methicillin-resistant Staphylococcus aureus (48% vs. 33.5%; P < .001), extended-spectrum β-lactamase-producing Escherichia coli (33% vs. 21%; P < .001), extended-spectrum β-lactamase-producing Klebsiella pneumoniae (30% vs. 20%; P < .001), and third-generation cephalosporin-resistant Acinetobacter baumanii (27% vs. 19%; P < .001) were also observed. Total costs saving were US$32,231 during the study period. Conclusions. Education and an antibiotic-control program constituted an effective and cost-saving strategy to optimize antibiotic use in a tertiary care center in Thailand.