BACKGROUND: Computerized clinical decision support systems (CDSS) have shown promising effectiveness in improving outpatient antibiotic prescribing. METHODS: We developed an intervention in the form of EPIC (Verona, WI, USA) order sets comprised of outpatient treatment pathways for 3 pediatric bacterial acute respiratory infections (ARIs) coupled with educational sessions. Four pediatric clinics were randomized into intervention and control arms over pre- and postimplementation study periods. In the intervention clinics, education was provided in between the 2 study periods and EPIC order sets became available at the beginning of the postimplementation period. The primary end point was the percentage of first-line antibiotic prescribing, and the secondary end points included antibiotic duration and antibiotic prescription modification within 14 days. RESULTS: A total of 2690 antibiotic prescriptions were included. During the pre-implementation phase, there was no difference in first-line antibiotic prescribing (74.9% vs 77.7%; P = .211) or antibiotic duration (9.69 ± 0.96 days vs 9.63 ± 1.07 days; P > .999) between the study arms. Following implementation, the intervention clinics had a higher percentage of first-line antibiotic prescribing (83.1% vs 77.7%; P = .024) and shorter antibiotic duration (9.28 ± 1.56 days vs 9.79 ± 0.75 days; P < .001) compared with the control clinics. The percentage of modified antibiotics was small in all clinics (1.1%-1.6%) and did not differ before and after the intervention (for all statistical comparisons, P ≤ .354). CONCLUSIONS: A computerized CDSS involving treatment pathways in the form of order sets coupled with educational sessions was associated with a higher percentage of first-line antibiotic prescribing and shorter antibiotic duration for the outpatient treatment of pediatric bacterial ARIs.