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Occlusion of the left atrial appendage (LAA) may protect against stroke in patients with atrial fibrillation. While percutaneous LAA closure devices have demonstrated efficacy in stroke reduction, surgical LAA occlusion has been performed with mixed results to date. Although surgical exclusion via internal sutures or noncutting stapler is ineffective due to recanalization of the LAA, surgical excision and certain exclusion devices including the AtriClip device are effective methods to achieve complete closure of the LAA. No data currently exists to support routine, prophylactic LAA closure at the time of cardiac surgery, but this practice may benefit certain patients at high risk for stroke. The currently enrolling Left Atrial Appendage Occlusion Study (LAAOS) III is the largest study to date designed to assess the efficacy of LAA occlusion for stroke prevention. The results of this trial will inform future clinical practice regarding stroke prevention with surgical LAA occlusion for patients with atrial fibrillation. Meanwhile, the ATLAS trial is investigating the efficacy of LAA occlusion in surgical patients who do not have atrial fibrillation but are at increased risk for developing it post-operatively.