Abstract Introduction Only a minority of operators in the MANIFEST-PF multinational survey performed superior vena cava isolation by means of pulsed field ablation (PFA). This is the first report of off-label PFA-mediated superior vena cava isolation in the presence of defibrillator leads. Purpose Aim of this study was to evaluate the effect of PFA applications in the superior vena cava in the terms of alterations in pacing, sensing, or impedance parameters, inappropriate anti-tachycardia pacing, ICD shock and leads dislodgment. Methods Five patients with a history of dilated cardiomyopathy, dual chamber defibrillator implantation, and worsening heart failure because of persistent atrial fibrillation (AF) underwent catheter ablation of AF. Three of the patients had dual coil defibrillator leads. PFA was selected for the index procedure in these decompensated heart failure patients with enlarged atria focusing beyond pulmonary vein isolation in posterior wall and roof ablation as well as in superior vena cava isolation. Results Basket configuration and two sets of two lesions at the trunk of the vessel (with rotation between each pair) were used for superior vena cava isolation in the presence of atrial and defibrillator leads, without any impact on device and leads measurements or sinus node function. All patients were in AF and cardioverted into sinus rhythm post- superior vena cava isolation. They remained at sinus rhythm at regular 3-month follow-up while device interrogation revealed intact sinus node function. Conclusion PFA applications in the superior vena cava of AF patients with implanted defibrillators confirmed that it is a safe and feasible method regardless of energy application adjacent to the leads.