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Atrial fibrillation ablation has historically been guided by fluoroscopy, with the related enhanced risk deriving from radiation. Fluoroscopy exposure may be confined to guide the transseptal puncture. Small sample size study presented a new methodology to perform a totally fluoroless atrial fibrillation ablation in the case of a patent foramen ovale (PFO). We evaluated this methodology in a large sample size of patients and a multicentre experience.Two hundred and fifty paroxysmal atrial fibrillation patients referred for first atrial fibrillation ablation with a CARTO3 electroanatomic mapping system were enrolled. In 58 out of 250 patients, a PFO allowed crossing of the interatrial septum, and a completely fluoroless ablation was performed applying the new method (Group A). In the remaining patients, a standard transseptal puncture was performed (Group B). Pulmonary vein isolation was achieved in all patients with comparable procedural and clinical outcomes at short- and long-term follow-up.The presence of a PFO may allow a completely fluoroless well tolerated and effective atrial fibrillation ablation. Probing the fossa ovalis looking for the PFO during the procedure is desirable, as it is not time-consuming and can potentially be done in every patient undergoing atrial fibrillation ablation.