The aims of the study were to verify the efficacy and safety of low energy internal cardioversion (LEIC) in patients with persistent atrial fibrillation (AF) and to identify the factors affecting the atrial defibrillation threshold (ADT). Forty-nine patients with persistent (lasting > or = 10 days) AF underwent LEIC. In each patient, two 6 Fr custom-made catheters with large active surface areas were positioned in the coronary sinus (cathode) and the lateral right wall (anode), respectively, for shock delivery, and a tetrapolar lead was placed in the right ventricular apex for R wave synchronization. Truncated, biphasic (3 ms + 3 ms), exponential shocks were used, beginning at 50 V and increasing in steps of 50 V until sinus rhythm had been restored. Mild sedation (diazepam 5 mg i.v.) was administered to 12 patients. Sinus rhythm was restored in all the subjects with mean voltage and energy levels of 352.0 +/- 80.3 V and 8.2 +/- 3.4 J, respectively. The ADT in patients pretreated with amiodarone (6.4 +/- 1.8 J) was lower than that of patients who had not received any antiarrhythmic drugs (9.2 +/- 3.7) (P = 0.04). No ventricular arrhythmias were induced by any of the atrial shocks, and no other complications were observed. During a mean follow-up of 162.9 +/- 58.7 days, AF recurred in 21 (43%) patients; 71% of these occurred in the first week after cardioversion. LEIC is effective in restoring sinus rhythm in patients with persistent AF. The technique seems to be safe and does not require general anesthesia or, in most cases, sedation. Patients pretreated with amiodarone have lower ADTs.