© 2015 American College of Cardiology Foundation PUBLISHED BY ELSEVIER INC. Objectives The purpose of this study was to assess the feasibility of pulmonary vein (PV) isolation using low-intensity collimated ultrasound. Background Contemporary approaches to PV isolation are limited by the technical complexity of mapping and ablation. We describe a novel approach to left atrial anatomic rendering and PV isolation that aims to overcome some of these limitations by using low-intensity collimated ultrasound (LICU) system, which allows for near real-time geometry creation and automated ablation in a porcine model. Methods Twenty swine were anesthetized, and the LICU ablation catheter was placed in the left atrium via percutaneous transseptal access. Ultrasound M-mode-based anatomies of the inferior PVs were successfully created, and ablation was performed under automatic robotic control along a user-defined lesion path. One animal was excluded because of device failure. Results All target PVs in the 19 remaining animals were isolated acutely, requiring a mean of 1.6 applications. Ten animals were sacrificed acutely, and the remaining 9 survived for 35 ± 11 days. Of these 9, 1 animal was excluded from analysis because the index lasso position could not be reliably recreated. PVs in 5 of 8 animals remained isolated at sacrifice. Of the 77 total histological sections, 62 lesions (80.5%) were noted to be transmural. Lesions were homogeneous and characterized by coagulative necrosis and fibrous tissue. The mean myocardial thickness was 2.66 ± 1.80 mm, and the mean lesion depth was 4.28 ± 1.97 mm. No extra cardiac or collateral lesions were noted. Conclusions This study demonstrates the safety and efficacy of a novel noncontact ultrasound mapping and ablation system to produce continuous transmural lesions that can isolate PVs in a porcine model.