In African-American (AA) adults, β-blockers (BB) have been reported to be less efficacious treating cardiac disease compared with whites (CAUC). This has been attributed to genetic polymorphisms of β-receptors. It is unknown if racial differences affect response to BB in pediatric patients with arrhythmias. AA and CAUC ≤ 18 years of age were included if they underwent treadmill stress testing while receiving metoprolol, atenolol, nadolol, or carvedilol. Patient demographics, resting heart rate (HR), maximum HR, and BB variables were collected. CAUC patients were matched on a 2:1 basis by age and sex to AA patients. Patients were blunted if HR was <90 % of maximum predicted HR for same-age patients on a modified Bruce protocol treadmill stress test. Long-term follow-up for breakthrough arrhythmias was documented. 78 patients were included (26 AA, 52 CAUC). No differences were noted in demographics, medication dose, BB or arrhythmia type, or baseline, maximal, or % HR change (p = not significant [NS]). On univariate analysis, fewer AA achieved a blunted HR during treadmill testing compared with CAUC (65 vs. 86%, p = 0.03). On multivariate analysis, AA were less likely to have an HR blunted by BB (OR 0.18, 95% confidence interval [CI] 0.04-0.75, p = 0.02) compared with CAUC. During the 1-year follow-up period, AA trended toward having one (58 vs. 40%, p = 0.14) or multiple instances (38 vs. 26%, p = 0.26) of breakthrough arrhythmia on cardiac Holter monitor testing. Race appears to affect the efficacy of BB therapy in pediatric patients with arrhythmias. Future studies to identify genetic polymorphisms in this patient subset are necessary.