Abstract Funding Acknowledgements Type of funding sources: None. Introduction Pulsed-field ablation (PFA) is a new non-thermal, tissue-specific ablation technique. Through the application of a local electric field, it is possible to induce a selective electroporation of cardiomyocytes membranes, resulting in myocytic apoptosis and sparing of non-myocardial structures (nerves, connective tissue, esophagus, vessels). Purpose A new PFA system for atrial fibrillation (AF) ablation has recently been introduced in our hospital. The aim of this retrospective review is to share the initial results of our experience in terms of acute efficacy and safety. Methods A total of 41 adult patients suitable for AF percutaneous ablation underwent PFA between April and November 2022 in our Institute. PFA system consisted of a current generator, a deflectable sheath and a multielectrode PFA catheter. Once inside the left atrium (LA), the PFA catheter was directed to the pulmonary veins (PVs) ostia through an over-the-wire system. Then, 8 electric impulses were applied for each PV to achieve electrical isolation; in some cases, applications to the posterior left atrium wall (LAPW) were delivered to obtain LAPW isolation (LAPWI). A moderate-to-deep sedation was provided by an anesthesiologist during all the procedures. Acute ablation efficacy was defined as absence of intracavitary signals at the electroanatomic mapping and local capture failure at the pacing maneuvers. Intra and peri-procedural safety was defined as the absence of major complications (pericardial effusion/ tamponade, stroke, vascular complications, death) during the procedure and the hospitalization period. Results Of the 41 patients included, 24 (58.5%) were treated for paroxysmal AF and 17 (41.5%) for persistent AF. In almost all cases (n=40, 97.6%) pulmonary veins isolation (PVI) was performed; in 14 cases (34.1%, almost all persistent AF patients) a LAPWI was performed with the application of a variable number of pulses (mean value = 13). In most of the cases (n=28, 68.3%) an electroanatomic mapping was acquired before and after the ablation. Acute efficacy was observed in all PVI cases (n=40, 100%) and in all LAPWI cases (n=14, 100%). No periprocedural major complications were observed (n=0, 0%). Conclusions PFA is a promising ablation technique capable of inducing selective myocytic apoptosis through electroporation, causing a thick damage across the muscle with no injury of other tissues, and could become a game changer in electrophysiology in the next future. Our initial data report a combination of ease of use and high efficacy and safety profiles.