Background Sotalol is a class III antiarrhythmic agent that is highly effective for tachyarrhythmias in adults, but its efficacy in patients with congenital heart disease (CHD) remains unclear. The purpose of this study was to assess the efficacy and safety of sotalol for refractory tachyarrhythmias in patients with CHD. Methods and Results Forty four-patients with CHD and refractory tachyarrhythmias (age, 23±12 years; follow-up period, 13±12 months) were administered sotalol orally during the period December 2002 to May 2007, resulting in complete control of tachyarrhythmias in 18 patients (41%), partial control in 15 patients (34%), and no control in 11 patients (25%). Non-pharmacological intervention (eg, surgery, pacemaker implantation, catheter ablation) was performed in 9 patients and resulted in an augmented response to sotalol in 6 patients. Tachyarrhythmia combined with atrial fibrillation was a risk factor for treatment failure with sotalol (odds ratio, 18.3; 95% confidence interval, 1.8-189.6; p=0.0053). Conclusion Sotalol is partially or completely effective for refractory tachyarrhythmias in patients with CHD, and non-pharmacological interventions improve the efficacy of sotalol. This multimodal approach should be considered in patients with refractory tachyarrhythmias and CHD. (Circ J 2008; 72: 1998 - 2003)