Background — The goal of this study was to test the hypothesis that the occurrence of atrial fibrillation (AF), in at least some patients with coexisting type I atrial flutter (AFL), is based on macro-reentry around the tricuspid valve orifice, including the right atrial (RA) isthmus, by evaluation of the AF recurrences after successful ablation of AFL. Methods and results — Eighty-two consecutive patients with type I AFL, with or without concomitant AF, underwent radiofrequency ablation (RFA) of the RA isthmus by an anatomical approach. The results were analyzed in 4 groups of patients: group 1 (only AFL; 29 patients), group 2 (AFL > AF; 22 patients), group 3 (AF > AFL; 15 patients), and group 4 (developing AFL while receiving class IC antiarrhythmic drug therapy for AF, the ‘class IC atrial flutter’; 16 patients). In all groups, RFA of type I AFL was performed with a high (≥ 93%) procedural success rate. In group 1, only 2 patients (8%) had AF after (18 ± 14 months) AFL ablation. These figures were 38% (20 ± 14 months) and 86% (13 ± 8 months) in groups 2 and 3, respectively. Group 4 patients (4 ± 2 months) had a 73% freedom of AF recurrences with continuation of the class IC agent. Conclusions — The low incidence of new AF during long-term follow-up after RFA of type I AFL makes it unlikely that radiofrequency lesions promote the development of AF. The impact of isthmus ablation on AF recurrences differs according to the clinically predominant atrial arrhythmia and suggests a possible role of the RA isthmus in the occurrence of AF in some patients. Ablation of class IC atrial flutter in patients with therapy-resistant AF is a novel approach to management of this patient subset. Careful classification of AF patients plays a role in the selection of the site of ablation therapy (Circulation 99: 1441-1445, 1999).