OBJECTIVE To characterize trends in outpatient antibiotic prescriptions in the United StatesDESIGN Retrospective ecological and temporal trend study evaluating outpatient antibiotic prescriptions from 2013 to 2015SETTING National administrative claims data from a pharmacy benefits manager PARTICIPANTS. Prescription pharmacy beneficiaries from Express Scripts Holding CompanyMEASUREMENTS Annual and seasonal percent change in antibiotic prescriptionsRESULTS Approximately 98 million outpatient antibiotic prescriptions were filled by 39 million insurance beneficiaries during the 3-year study period. The most commonly prescribed antibiotics were azithromycin, amoxicillin, amoxicillin/clavulanate, ciprofloxacin, and cephalexin. No significant changes in individual or overall annual antibiotic prescribing rates were found during the study period. Significant seasonal variation was observed, with antibiotics being 42% more likely to be prescribed during February than September (peak-to-trough ratio [PTTR], 1.42; 95% confidence interval [CI], 1.39-1.61). Similar seasonal trends were found for azithromycin (PTTR, 2.46; 95% CI, 2.44-3.47), amoxicillin (PTTR, 1.52; 95% CI, 1.42-1.89), and amoxicillin/clavulanate (PTTR, 1.78; 95% CI, 1.68-2.29).CONCLUSIONS This study demonstrates that annual national outpatient antibiotic prescribing practices remained unchanged during our study period. Furthermore, seasonal peaks in antibiotics generally used to treat viral upper respiratory tract infections remained unchanged during cold and influenza season. These results suggest that inappropriate prescribing of antibiotics remains widespread, despite the concurrent release of several guideline-based best practices intended to reduce inappropriate antibiotic consumption; however, further research linking national outpatient antibiotic prescriptions to associated medical conditions is needed to confirm these findings.