To evaluate the safety and efficacy of catheter mediated radiofrequency (RF) ablation in patients with Wolff-Parkinson-White syndrome, 125 patients with accessory pathway (AP) mediated tachyarrhythmias underwent RF ablation. Right-sided APs were ablated from the atrial aspect of the tricuspid annulus (all from the femoral vein approach) and the left-sided APs were ablated from the atrial or ventricular aspect of the mitral annulus. Immediately after ablation, 3 of 8 APs (38%) and 131 of 137 APs (95%) were ablated successfully with RF through a small-tip (2 mm) and a large-tip (4 mm) electrode catheter, respectively. Seven of the 11 APs where RF ablation failed had a later successful DC ablation. During follow-up (3 to 22 months), 11 of the 114 patients (10%) with successful ablation had return of accessory pathway conduction (2 had recurrence of tachycardia (2%)). Complications included transient myocardial injury (peak CK-MB 15 +/- 3 IU/l), transient proarrhythmic effects (more atrial and ventricular premature beats), accidental AV block (1 patient), cardiac tamponade (1 patient) and suspicion of aortic dissection (1 patient). In successful sessions, procedure and radiation exposure time were 3.8 +/- 0.2 h and 45 +/- 4 min, respectively. This study confirms that RF ablation with a large-tip electrode catheter is an effective and relatively safe nonsurgical method for treatment of Wolff-Parkinson-White syndrome.