BACKGROUND: This study investigates differences in antibiotic prescribing rates for pediatric upper respiratory infections (URIs) between physicians and nurse practitioners (NPs). METHODS: Visits by children <18 years old diagnosed with URI to physicians or NPs between 2001 and 2010 were abstracted from the National Ambulatory Medical Care Survey and National Hospital Ambulatory Care Survey. Logistic regression analyses examined variations in antibiotic prescribing rates. RESULTS: Upper respiratory infections accounted for approximately 439 +/- 21.5 million visits. Patients seen by NPs were more likely to have Medicaid, live in the lowest median household income quartile zip codes and micropolitan locations, and live in the South compared to patients seen by physicians. Nurse practitioners prescribed antibiotics 66.7% +/- 4.2% of the time versus physicians at 52.8% +/- 0.8% for URI visits (unadjusted P-value = .002). Adjusted by specialty, URI type, and chronic diseases, NPs had marginally significantly different odds of prescribing antibiotics (OR = 1.6, 95% CI, 1.0-2.6, P-value = .048), but the association with prescribing broad-spectrum antibiotics is not as strong (adjusted P-value = .063). Patient visits to a pediatric (OR = 0.54, 95% CI, 0.43-0.67) or ENT/surgery practice (OR = 0.11, 95% CI, 0.06-0.18) had lower odds of antibiotic prescribing compared to general/family medicine practices. Year (2001-2010) was not significantly associated with antibiotic or broad-spectrum antibiotic prescribing rates for physicians, but rates for NPs fell for otitis media (P-value = .007) from 90.2% +/- 8.2% (2001-2002) to 74.8% +/- 6.8% (2009-2010) of visits. CONCLUSIONS: Nurse practitioners have higher rates of antibiotic prescribing compared to physicians for pediatric patients with URIs; however, this difference is less after adjusting for specialty. Examining comparative antibiotic prescribing is important to promote evidence-based practice and adoption of clinical guidelines.