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Background With regards to short-term outcome in atrial fibrillation (AF), the benefit of cryoballoon ablation (CBA) by pressing a balloon against the earliest pulmonary vein (PV) potential site during pulmonary vein isolation, (earliest potential [EP]-guided CBA) has been previously demonstrated. Objective The present study aimed to evaluate the long-term outcome of the EP-guided CBA. Methods This study included 136 patients from two randomized studies, who underwent CBA for paroxysmal AF for the first time. Patients were randomly assigned to the EP-guided and conventional CBA groups in each study. In the EP-guided CBA group, we pressed a balloon against the EP site when the time to isolation (TTI) after cryoapplication exceeded 60 s and 45 s in the first and second studies, respectively. The patients were followed up for 1 year after procedure. We compared the clinical outcomes between the EP-guided CBA group (68 patients) and the conventional CBA group (68 patients). Results No significant differences in baseline characteristics were observed between the two groups. Compared with the conventional CBA group, the EP-guided CBA group had a significantly higher success rate at TTI ≤90 s (98.5% vs. 90.0%, P<0.001); lower touch-up rate and total cryoapplication; and shorter procedure time, and fluoroscopy time. The recurrence at 1-year after ablation was significantly lower in the EP-guided CBA group than in the conventional CBA group (6.0% vs. 19.4%; P=0.019). Conclusions The EP-guided CBA approach can facilitate the ablation procedure and achieve low recurrence at 1-year after ablation. FUNDunding Acknowledgement Type of funding sources: None. Earliest potential [EP]-guided CBA The recurrence at 1-year after ablation