Introduction : Pulsed field ablation (PFA) is a non-thermal ablative strategy that achieves cell death via electroporation. Herein, we investigated the preclinical safety and efficacy of PFA using two novel 8-French, 16-electrode spiral PFA/mapping catheters (ElePulse, CRC EP, Inc). M ethods : Bipolar PFA (>1.8 kV) was performed using 30 sec, single-shot, QRS-gated applications. Altogether, 94 atrial structures were ablated in 23 swine, 1 canine, and 1 ovine, including right and left atria and atrial appendages, pulmonary veins, and superior and inferior (IVC) vena cavae. We also examined the impact of PFA on phrenic nerve (14 swine) and on a deviated esophagus after delivery of PFA from inside the IVC (5 swine). Results: All applications were single-shot without catheter repositioning. Minimal microbubbling was observed without significant skeletal muscle twitching/activation (mean acceleration: 0.05 m/s ²). There was marked reduction in post- versus pre-PFA atrial electrogram amplitude (0.17±0.21 mV vs. 1.18±1.08 mV; P<0.0001). Durable conduction block was demonstrated up to 3 months in all targeted tissues. Lesions were contiguous and transmural, measuring 25±9 mm x 21±7 mm without any thermal effects. Magnetic resonance, gross, and histologic examinations of the brain, rete mirabile, and kidneys revealed no thromboembolism. No acute/long-term phrenic nerve dysfunction was encountered. Though within 2 hours of ablation, histologic examinations of the esophagus revealed acute PFA-related changes in the muscular layer, these completely resolved by 21±5 days. Conclusion : A novel, single-shot, spiral PFA system is capable of safely creating large, durable atrial lesions without significant adverse effects on the phrenic nerve or the esophagus.