© 2015 American College of Physicians. Background: Despite efforts to reduce antibiotic prescribing for acute respiratory infections (ARIs), information on factors that drive prescribing is limited. Objective: To examine trends in antibiotic prescribing in the Veterans Affairs population over an 8-year period and to identify patient, provider, and setting sources of variation. Design: Retrospective, cross-sectional study. Setting: All emergency departments and primary and urgent care clinics in the Veterans Affairs health system. Participants: All patient visits between 2005 and 2012 with primary diagnoses of ARIs that typically had low proportions of bacterial infection. Patients with infections or comorbid conditions that indicated antibiotic use were excluded. Measurements: Overall antibiotic prescription; macrolide prescription; and patient, provider, and setting characteristics extracted from the electronic health record. Results: The proportion of 1 million visits with ARI diagnoses that resulted in antibiotic prescriptions increased from 67.5% in 2005 to 69.2% in 2012 (P < 0.001). The proportion of macrolide antibiotics prescribed increased from 36.8% to 47.0% (P < 0.001). Antibiotic prescribing was highest for sinusitis (adjusted proportion, 86%) and bronchitis (85%) and varied little according to fever, age, setting, or comorbid conditions. Substantial variation was identified in prescribing at the provider level: The 10% of providers who prescribed the most antibiotics did so during at least 95% of their ARI visits, and the 10% who prescribed the least did so during 40% or fewer of their ARI visits. Limitation: Some clinical data that may have influenced the prescribing decision were missing. Conclusion: Veterans with ARIs commonly receive antibiotics, regardless of patient, provider, or setting characteristics. Macrolide use has increased, and substantial variation was identified in antibiotic prescribing at the provider level. Primary Funding Source: U.S. Department of Veterans Affairs, Centers for Disease Control and Prevention.