OBJECTIVE In patients with cavotricuspid isthmus (CTI) ablation for atrial flutter (AFL), the decision to hold oral anticoagulation (OAC) often becomes an issue. The purpose of this study was to describe the incidence of the development of atrial fibrillation (AF) after CTI ablation in patients with documented AFL with and without a previous history of AF and to identify risk predictors for the occurrence of AF after CTI. RESULTS We included 364 consecutive patients undergoing successful CTI ablation. Thereof, 230 patients (170 male; age 66 ± 11 years) had AFL only (AFL group) and 134 patients (94 male; age 65 ± 11 years) had AFL and previously documented AF (AFL and AF group). Over a mean follow-up of 22 ± 20 months, 163 (71%) patients in the AFL group and 67 (50%) patients in the AFL and AF groups had no documentation of a recurrent atrial arrhythmia (P < 0.001). AF developed in 51 patients (22%) in the AFL group and in 57 (43%) patients in the AFL and AF groups (P < 0.001). In patients without history of AF, left atrial diameter was the only predictor of development of AF (HR 1.058 [95%CI 1.011-1.108], P = 0.016). Multivariate analysis of the total population identified history of AF (HR 1.918 [95%CI 1.301-2.830], P = 0.001) and BMI as predictors for AF development (HR 1.052 [95%CI 1.012-1.093], P = 0.011). CONCLUSIONS Our results indicate that new-onset AF develops in a significant proportion of patients undergoing CTI for AFL. One should therefore be careful to withhold OAC. Furthermore, pulmonary vein isolation should be considered in conjunction with CTI, particularly in patients with previously documented AF.