BACKGROUND: Anti-influenza antiviral medications reduce influenza-related morbidity, but may often be used inappropriately. OBJECTIVE: To measure the rate of antiviral and antibiotic prescribing, the appropriateness of antiviral prescribing, and evaluate independent predictors of antiviral and antibiotic prescribing for influenza in primary care. DESIGN AND PATIENTS: Retrospective analysis of 958 visits of clinician-diagnosed influenza in 21 primary care clinics in eastern Massachusetts from 1999 to 2007. We considered antiviral prescribing appropriate if patients had symptoms for 2 or fewer days, had fever, and any 2 of headache, sore throat, cough, or myalgias. MEASUREMENTS AND MAIN RESULTS: Clinicians prescribed antivirals in 557 (58%) visits and antibiotics in 104 visits (11%). Of antiviral prescriptions, 38% were not appropriate, most commonly because of symptoms for more than 2 days (24% of antiviral prescriptions). In multivariate modeling, selected independent predictors of antiviral prescribing were symptom duration of 2 or fewer days (odds ratio [OR], 12.4; 95% confidence interval [CI], 8.3 to 18.6), year (OR, 1.4 for each successive influenza season; 95% CI, 1.3 to 1.7), patient age (OR, 1.3 per decade; 95% CI, 1.2 to 1.5), and, compared to having no influenza testing, having a negative influenza test (OR, 5.5; 95% CI, 3.4 to 9.1) or a positive influenza test (OR, 11.4; 95% CI, 6.7 to 19.3). Independent predictors of antibiotic prescribing included otoscopic abnormalities (OR, 3.3; 95% CI, 1.8 to 6.0), abnormal lung examination (OR, 4.0; 95% CI, 2.1 to 6.2), and having a chest x-ray performed (OR, 2.2; 95% CI, 1.3 to 3.8). CONCLUSIONS: Primary care clinicians are much more likely to prescribe antivirals to patients with symptoms for 2 or fewer days, but also commonly prescribe antivirals inappropriately.