<p>Antibiotic stewardship programs proved to be effective in improving prescribing appropriateness. This multicenter quasi-experimental study, aimed to assesses the stewardship impact on antibiotics prescribing in different semesters from 2014 to 2019 in three pediatric emergency departments (Center A, B, and C) in Italy. All consecutive patients diagnosed with acute otitis media or pharyngitis were evaluated for inclusion. Two different stewardship were adopted: for Center A and B, clinical pathways were implemented and disseminated, and yearly lectures were held, for Center C, only pathways were implemented. Broad-spectrum prescription rates decreased significantly by 80% for pharyngitis and 29.5 to 55.2% for otitis after the implementation. In Center C, rates gradually increased from the year after the implementation. Amoxicillin dosage adjusted to pharyngitis recommendations in Center C (53.7 vs. 51.6 mg/kg/die; = 0.011) and otitis recommendations in Center A increasing from 50.0 to 75.0 mg/kg/die ( &lt; 0.001). Days of therapy in children &lt; 24 months with otitis increased from 8.0 to 10.0 in Center A, while in older children decreased in Center A (8.0 vs. 7.0; &lt; 0.001) and Center B (10.0 vs. 8.0; &lt; 0.001). Clinical pathways combined with educational lectures is a feasible and sustainable program in reducing broad-spectrum antibiotic prescribing with stable rates over time.</p>