Context: Data on the efficacy of β-blockers in the 3 most common genetic long QT syndrome(LQTS) loci are limited. Objective: To describe and assess outcome in a large systematically genotyped population of β-blocker treated LQTS patients. Design, Setting, and Patients: Consecutive LQTS-genotyped patients(n=335) in Italy treated with β-blockers for an average of 5 years. Main Outcome Measures: Cardiac events(syncope, ventricular tachycardia/torsades de pointes, cardiac arrest, and sudden cardiac death) while patients received β-blocker therapy according to genotype. Results: Cardiac events among patients receiving β-blocker therapy occurred in 19 of 187(10%) LQT1 patients, 27 of 120(23%)LQT2 patients, and 9 of 28(32%)LQT3 patients(P< .001). The risk of cardiac events was higher among LQT2(adjusted relative risk, 2.81; 95%confidence interval,1.50-5.27;P=.001) and LQT3 (adjusted relative risk, 4.00; 95%CI, 2.45-8.03; P< .001) patients than among LQ77 patients, suggesting inadequate protection from β-blocker therapy. Other important predictors of risk were a QT interval corrected for heart rate that was more than 500 ms in patients receiving therapy(adjusted relative risk, 2.01; 95%CI, 1.16-3.51; P=.01) and occurrence of a first cardiac event before the age of 7 years (adjusted RR, 4.34; 95%CI, 2.35-8.03; P< .001). Conclusion: Among patients with genetic LQTS treated with β-blockers, there is a high rate of cardiac events, particularly among patients with LQT2 and LQT3 genotypes. Context: Data on the efficacy of β-blockers in the 3 most common genetic long QT syndrome (LQTS) loci are limited. Objective: To describe and assess outcome in a large systematically genotyped population of β-blocker treated LQTS patients. Design, Setting , and Patients: Consecutive LQTS-genotyped patients (n = 335) in Italy treated with β-blockers for an average of 5 years. Main Outcome Measures: Cardiac events (syncope, ventricular tachycardia / torsades de pointes, cardiac arrest, and sudden cardiac Results: Cardiac events among patients receiving β-blocker therapy occurred in 19 of 187 (10%) LQT1 patients, 27 of 120 (23%) of LQT2 patients, and 9 of 28 (32%) LQT3 patients (P <.001). The risk of cardiac events was higher among LQT2 (adjusted relative risk, 2.81; 95% confidence interval, 1.50-5.27; P = .001) and LQT3 4.00; 95% CI, 2.45-8.03; P <.001) patients than among LQ77 patients, Prov. Inadequate p rotection from β-blocker therapy. Other important predictors of risk were a QT interval corrected for heart rate that was more than 500 ms in patients receiving therapy (adjusted relative risk, 2.01; 95% CI, 1.16-3.51; P = .01) and occurrence of a first cardiac event before the age of 7 years (adjusted RR, 4.34; 95% CI, 2.35-8.03; P <.001). Conclusion: Among patients with genetic LQTS treated with β-blockers, there is a high rate of cardiac events, particularly among patients with LQT2 and LQT3 genotypes.