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This study examined whether a significant change in antibiotic use caused by an Australian government directive targeted at amoxicillin with clavulanic acid (AC) was associated with changes in prescription share, health care costs, and patient outcomes. We used an integrated database of computerized general practice medical records, which included data regarding 34,242 patients and 318,234 recorded patient visits. There were 15,303 antibiotic prescriptions provided to 9921 patients during a 4-year period, with AC prescribed for 1453 (14.6%) of these patients. A total of 5125 patient outcomes were identified. There was a shift away from best-practice antibiotic prescribing, and a significant association was identified between the rate and cost of process-of-care and patient outcomes and the decrease in AC-prescription share. This policy initiative created unintended changes in prescribing behavior, increased costs to the government, and a trend toward poorer patient outcomes. Detailed analyses are required before instigating initiatives aimed at changing clinicians' prescribing behavior.