Abstract Background Cryo-ablation for persistent atrial fibrillation (PeAF) has been reported to be safe and comparable to radiofrequency (RF) ablation, but the outcome was not satisfactory. AF drivers mapping after pulmonary vein isolation (PVI) was reported to be widely identified in left atrium (LA). On the other hand, extensive drivers ablation is considered to have limited durability of PVI compared to cryo-ablation. Purpose This study sought to investigate the efficacy and safety of additional PV antrum substrate ablation after PVI by cryo-ablation in patients with PeAF. Methods A total of 122 consecutive patients (90 men, 32 women) who underwent ablation between January 2021 and July 2023 for PeAF, except for patients with long standing ≥10years AF, or large LA diameter ≥55mm, or low left ventricular ejection fraction (LVEF) ≤35% with organic heart disease, were divided into three groups; cryo-ablation alone (Cryo group; 30 patients), RF ablation alone guided by AF drivers mapping (RF group; 52 patients), or cryo-ablation plus RF for AF drivers (Cryo+RF group; 40 patients). AF drivers mapping was performed by real-time phase mapping system or complex fractionated electrograms (Figure1). The outcome of freedom from atrial tachy-arrhythmia lasting longer than 30 seconds without anti-arrhythmic drugs after three months blanking period of a single procedure was compared among groups. Results Baseline characteristics of patients (68±9.2 years old, LVEF 57±9.9 %, LA diameter 43±5.4 mm, persistent AF duration 9.4±18 months, long standing ≥1year AF 17 patients) were similar in three groups. The incident of recurrence of atrial tachy-arrhythmia in Cryo+RF group was significantly lower compared with Cryo group (15% vs. 37%; p=0.014) and RF group (15% vs. 25%; p=0.28) (Figure2). There was no serious complication in three groups. Conclusion Additional drivers RF ablation after cryo-ablation for PeAF is safe and associated with a significant reduction in atrial tachy-arrhythmia recurrence.Figure 1Figure 2