BACKGROUND: Left atrial appendage (LAA) electrical isolation is reported to improve atrial fibrillation ablation outcomes. However, loss of mechanical function may increase thromboembolic risk. OBJECTIVE: The aim of this study was to evaluate the feasibility and safety of LAA occlusion after electrical isolation in a canine model. METHODS: Nine canines underwent LAA isolation with irrigated radiofrequency ablation after pulmonary vein (PV) isolation. Entrance and exit block were confirmed with intravenous adenosine after 30 minutes. The LAA was then occluded with a Watchman device. Device position was assessed at 10 days by using transthoracic echocardiography. At 45 days, LAA isolation was assessed epicardially. Hearts were then examined macroscopically and histologically. RESULTS: All 36 PVs and 8 of 9 LAAs (89%) were electrically isolated. Acute LAA reconnection occurred in 4 of 8 LAAs (50%). All were reisolated. The mean ablation time was 51 ± 19 minutes, including 24 ± 18 minutes for LAA isolation. LAA occlusion was successful in all cases. One animal died of a primary intracranial bleed due to anticoagulant hypersensitivity 36 hours after the procedure. Transthoracic echocardiography at 10 days confirmed satisfactory device positions and no pericardial effusion. At 45 days, 7 of 8 (88%) had persistent LAA electrical isolation. All devices were stable without evidence of erosion. Microscopy revealed complete device-tissue apposition and a mature connective tissue layer overlying the device surface in all cases. CONCLUSION: LAA electrical isolation and mechanical occlusion can be performed concomitantly in this animal model, with no displacement or mechanical erosion of the appendage at 45 days. This technique can potentially improve success rates and obviate the need for chronic anticoagulation. Future studies should address efficacy, safety, and feasibility in humans.