OBJECTIVE Electrical cardioversion (CV) is used to restore sinus rhythm (SR) in patients with atrial fibrillation (AF). In this prospective randomized study, we compared two different methods of electrical CV, namely transthoracic (TT) and low-energy transvenous internal CV (ICV), in patients with persistent AF with respect to efficacy, safety and the magnitude of myocardial damage provoked by either method. RESULTS Fifty-two patients with persistent AF were randomly assigned to either TT (n = 26) or ICV (n = 26). The baseline characteristics of the two treatment groups were similar. TT CV was performed under sedation with hand-held electrodes in the apex-anterior position and high-energy (100-360J) monophasic shocks. ICV was performed by a single catheter approach utilizing a special balloon-directed catheter with proximal and distal arrays of shock electrodes that were positioned in the right atrium and left pulmonary artery under fluoroscopy. Truncated, biphasic shocks of low energy (1-15 joules) were used. Cardiac troponin T (cTpnT), creatine kinase (CK) and CK-MB levels were assessed before and 24 hours after each procedure. SR was restored in 24/26 (92%) patients in the ICV and 22/26 (85%) patients in the TT CV groups (p > 0.05). The mean energy to achieve SR was significantly higher with the TT method (9.8 +/- 4.3 J vs. 246.4 +/- 73.6 J, p < 0.05). CV with either method caused no elevation in cTpnT levels. Total CK and CK-MB levels remained unchanged with ICV. On the other hand, TT CV resulted in a significant increase in total CK (51.8 +/- 30 vs. 156.5 +/- 255.3, p < 0.05) and a nonsignificant rise in CK-MB levels (14.7 +/- 7 vs. 17.3 +/- 1.1, p > 0.05). CONCLUSIONS In this prospective randomized comparison, TT and ICV were found to be equally effective to restore SR in patients with persistent AF No evidence of myocardial damage was detected with either method.