Study ObjectivesTo compare vancomycin trough concentrations in overweight or obese pediatric patients to those with normal body habitus, after initial dosing based on total body weight (TBW).DesignRetrospective observational case‐control study.SettingFree‐standing academic pediatric hospital.PatientsForty‐two overweight or obese pediatric patients were matched to 84 children of normal body habitus (NBH).Measurements and Main ResultsEmpiric vancomycin dosing was based on TBW and guided by an age‐stratified dosing algorithm previously developed at our center. Initial steady‐state vancomycin trough concentrations were retrieved from the electronic medical record. Overweight and obese children had significantly higher initial vancomycin trough concentrations compared with children who had an NBH (median 14.4 μg/ml vs 10.5 μg/ml, p<0.001). Initial vancomycin trough concentrations above 20 μg/ml occurred more often in overweight and obese children (p=0.016). Our dosing algorithm suggested that initial vancomycin trough concentrations below 10 μg/ml occurred significantly more often in children with NBH (p<0.001).ConclusionsOverweight and obese pediatric patients may have elevated initial vancomycin trough concentrations when empiric dosing is based on TBW. Special attention to therapeutic drug monitoring is warranted in all children.