Aims Direct current cardioversion of persistent atrial fibrillation is one of the most widely used and effective treatments for the restoration of sinus rhythm, but may be hampered by a low success rate and a high percentage of early recurrence. pre-treatment with amiodarone or a glucose-insulin-potassium solution could improve the efficacy of electrical cardioversion by reversing the partially depolarized diastolic potential of the subsidiary pacemakers in atrial fibrillation. In a controlled randomized study, we assessed the effectiveness of electrical cardioversion in patients with persistent atrial fibrillation after pre-treatment with amiodarone or potassium infusion and the efficacy of amiodarone in maintaining sinus rhythm after electrical cardioversion. Methods and Results Ninety-two patients with persistent atrial fibrillation (>2 weeks duration) were prospectively randomized into three matched groups: A (n=31, oral amiodarone 400 mg. day(-1) 1 month before and 200 mg.day(-1) 2 months after cardioversion), B (n=31, 180 mg.day(-1) oral diltiazem 1 month before and 2 months after cardioversion and 80 mmol potassium, 50 UI insulin in 500 mi 30%;, glucose solution 24 h before cardioversion) and C (n=30, control patients, 180 mg. day(-1) oral diltiazem 1 month before and 2 months after cardioversion). Before cardioversion all patients were under 4 weeks effective oral anticoagulant therapy (warfarin). Before electrical cardioversion, the rate of spontaneous conversion to sinus rhythm was higher in group A (25%) than groups B (6%) or C (3%) (P<0.005). Electrical cardioversion was more successful in group A (88%) than groups B (56%) or C (65%) (P<0.05), while the electrical thresholds for effective cardioversion were lower in group B than the other groups (P<0.05). Twenty-four hours after cardioversion, the early recurrence of atrial fibrillation was similar in the three groups (P=ns), while at 2 months the recurrence rate was lower in group A (32%) than groups B (56%) or C (52%) (P<0.01). Conclusion Pre-treatment with low-dose oral amiodarone, compared with oral diltiazem or glucose-insulin-potassium treatments, induces a significantly high percentage of instances of spontaneous conversion, increases electrical cardioversion efficacy and reduces atrial fibrillation recurrence. (Eur Heart J 2000; 21: 66-73) (C) 2000 The European Society of Cardiology.