BACKGROUND: Pulsed-field ablation (PFA) is a novel ablation energy source, which leads to selective and irreversible electroporation of cardiomyocytes with no collateral damage to adjacent tissues. The presence of mechanical prosthetic valves may pose some issues related to catheter manipulation and risk of electromagnetic interference. OBJECTIVES: The purpose of this study was to assess the feasibility of PFA in patients with mechanical prosthetic valves. METHODS: The authors enrolled 30 consecutive patients (age 64.7 ± 11.4 years; 43% men) with mitral and/or aortic valve replacement with mechanical substitutes undergoing endocardial AF ablation via a PFA technology at 6 institutions. RESULTS: Time between valve surgery and ablation was 6.6 ± 6.5 years; 14 (46.7%) patients had an aortic mechanical valve, 10 (33.3%) a mitral, and 6 (20.0%) both. The following PFA technologies were used: FARAWAVE in 25 patients, Sphere-9 in 2, PulseSelect in 2, and the CENTAURI System in 1. No periprocedural and 1-month postablation major and minor complications were observed. Postprocedural transthoracic echocardiography did not identify any prosthetic valve dysfunction. One patient showed electromagnetic interference of the PFA catheter adjacent to the mitral prosthesis without clinical implications. No energy delivery to the mitral edge of the isthmus was possible despite multiple attempts to reposition the catheter. Mean procedural time was 77.5 ± 29.9 minutes, whereas mean left atrial dwell and fluoroscopy times were 43.1 ± 21.4 and 14.0 ± 6.4 minutes, respectively. CONCLUSIONS: PFA in patients with mechanical valves appears safe, but careful catheter handling is essential to avoid electromagnetic interference hindering PFA delivery.