OBJECTIVE : The usefulness and mechanisms of antiarrhythmic drug (AAD) pre-treatment as a facilitator of the acute success of electrical cardioversion (ECV) in atrial fibrillation (AF) remain controversial. We sought to analyze the role of AAD treatment with this purpose, differentiating its possible utility either facilitating the restoration of sinus rhythm (SR) or reducing immediate AF recurrences (IAFR). METHODS : We analyzed 2962 consecutive patients with persistent AF undergoing ECV prospectively included in 3 national registries. The acute success of ECV was indicated by the reversion to SR without presenting an IAFR (< 2 h). RESULTS : A total of 1410 patients (48%) received AAD treatment prior to ECV (80% amiodarone, 15% class Ic AAD, 2% other AAD). The rate of restoration of SR was similar between the patients treated with amiodarone (92%), class Ic AAD (91%) and who did not receive AAD pre-treatment (91%) (p = 0.92). However, those treated with amiodarone had fewer IAFR than those in the other two groups (amiodarone 3% vs class Ic 7% vs without treatment 6%; p = 0.002), so the ECV success rate was higher in the amiodarone group than in the other groups (amiodarone 89% vs Ic 84% vs without treatment 86%; p = 0.04). After adjusting for multiple variables, amiodarone remained as an independent predictor of a lower occurrence of IAFR (OR = 0.57; p = 0.01) and of a successful ECV (OR 1.37; p = 0.01). CONCLUSIONS : For patients with persistent AF undergoing ECV, AAD has a neutral effect on the restoration of SR but amiodarone increases its effectiveness due to a lower incidence of IAFR.