BACKGROUND: U.S. recommendations for using influenza antiviral medications changed in response to viral resistance (to reduce adamantane use) and during the 2009 H1N1 pandemic (to focus on protecting high-risk patients). Little information is available on clinician adherence to these recommendations. We characterized population-based outpatient antiviral medication usage, including diagnosis and testing practices, before and during the pandemic. METHODS: Eight medical care organizations in the Vaccine Safety Datalink Project provided data on influenza antiviral medication dispensings from January 2000 through June 2010. Dispensing rates were explored in relation to changes in recommendations and influenza diagnosis and laboratory testing frequencies. Factors associated with oseltamivir dispensings in pandemic versus pre-pandemic periods were identified using multivariable logistic regression. RESULTS: Antiviral use changed coincident with recommendations to avoid adamantanes in 2006, to use alternatives to oseltamivir in 2008, and to use oseltamivir during the pandemic. Of 38,019 oseltamivir dispensings during the pandemic, 31% were to patients not assigned an influenza diagnosis, and 97% were to patients not tested for influenza. Oseltamivir was more likely to be dispensed in pandemic versus pre-pandemic periods to patients <25 years old and to those with underlying conditions, including chronic pulmonary disease or pregnancy (P<0.0001 for each factor in multivariable analysis). CONCLUSIONS: Antiviral medication usage patterns suggest that clinicians followed recommendations to change antiviral prescribing based on resistance and to focus on high-risk patients during the pandemic. Medications were commonly dispensed to patients without influenza diagnoses and tests, suggesting that antiviral dispensings may offer useful supplemental data for monitoring influenza incidence.