Background: Pulsed field ablation (PFA) is a non-thermal energy source with promising safety and efficacy advantages. We aimed to develop a convenient, safe, effective and fast method of pulmonary vein isolation (PVI) utilizing a penta-spline PFA catheter via a single femoral vein and a venous closure system.Methods and Results: Consecutive patients (n=50; mean age: 63.6±10.7 years, 38% female) presenting with AF (paroxysmal AF: 56%) underwent first-time PVI via PFA. A single ultrasound-guided femoral vein puncture and a single transseptal puncture were used. After PVI using the penta-spline PFA catheter, extra pulse trains were added to the posterior wall for wide antral circumferential ablation. A venous closure system was used and a Donati suture was performed. The pressure bandage was removed after 1 h. A total of 196 PVs were identified and isolated with PFA only. The mean procedural time was 27.4±6.6 min, and the mean dwelling time was 14.4±5.5 min. Time to ambulation was 3.3±3.1 h. No severe complications occurred. During a mean follow-up of 6.5±2.1 months, 41/50 patients (82%) remained in sinus rhythm.Conclusions: The combination of a single venous puncture, single transseptal puncture approach using PFA and vascular closure device resulted in a 100% rate of acute PVI and an extraordinarily fast procedure and time to ambulation. The rate of periprocedural complications was low.