Aims - Although less common, typical atrial flutter (AFL) shares similar pathophysiologic roots with atrial fibrillation (AF). Following successful cavo-tricuspid isthmus ablation using radiofrequency (RF), many patients, however, develop AF in the mid-to-long-term. This study sought to assess whether pulmonary vein isolation (PVI) conducted at the same time as cavo-tricuspid isthmus ablation would significantly modify the AF burden upon follow-up (FU) in patients suffering from typical AFL. Methods - This was a multicenter randomized controlled study involving AFL patients with history of non-predominant AF (1 AF episode only in 67% of population) who were scheduled for CTI RF ablation. Patients were randomly assigned to either undergo cavo-tricuspid isthmus (CTI) ablation alone or CTI plus PVI (CTI+). PVI was performed using cryoballoon technology. An outpatient consultation with ECG and 1-week Holter monitoring was performed at 3, 6 months, 1 year, and 2 years post-procedure. The primary endpoint was AF recurrences lasting more than 30 s at 2 years post-ablation. Results - Of the patients enrolled, 36 were included in each group. At 2-year FU, the AF recurrence rate was significantly higher in the CTI versus CTI+ group (25/36, 69% vs. 12/36, 33% respectively; p<0.001), with similar AFL recurrence rates. There were no differences in quality of life or undesirable events, except for transient phrenic nerve palsy reported from three PVI patients (8.3%). Conclusion - PVI using cryoballoon technology was proven to significantly reduce the AF incidence at 2 years post-CTI-ablation.