Supraventricular tachycardias (SVTs) are a major cause of morbidity in adults with congenital heart disease (CHD). Few data exist on safety and efficacy of antiarrhythmic drugs in this population. Our aim was to determine the efficacy of antiarrhythmic drugs in adults with CHD and first-onset SVT on maintaining sinus rhythm after conversion. This was a multicenter retrospective study including adults with CHD and first-onset SVT from January 2008 to January 2011. First-onset SVT occurred in 92 of 7,171 patients without previous SVT (mean age 51 ± 16 years, 57% women). SVTs included atrial fibrillation and flutter in >80% of the patients. Most of these patients had septal defects (50%) and left-sided lesions (21%). The acute management of SVTs resulted in sinus rhythm in 83 patients, and 89% of these patients were instituted on oral antiarrhythmics to prevent SVT recurrence. After a mean follow-up of 2.5 ± 1.4 years, only 45% of the patients were free from SVT. Class III antiarrhythmics (85% sotalol and 15% amiodarone) were associated with a significantly lesser risk of SVT recurrence compared with all other antiarrhythmic drugs (hazard ratio 0.5, 95% confidence interval 0.27 to 0.96, p = 0.036). However, adverse effects of medication occurred in 22% of the patients, mainly in patients taking amiodarone. In conclusion, in adults with CHD and first-onset SVTs, class III antiarrhythmics are more efficacious in maintaining sinus rhythm after cardioversion than other antiarrhythmics. Sotalol may be considered as the first-choice therapy as this is associated with fewer adverse effects than amiodarone.