ABSTRACT. The left atrial appendage (LAA) is implicated as a source of thrombus in the majority of patients with atrial fibrillation (AF) and embolic stroke. Therapeutic anticoagulation (AC) is the mainstay of treatment for stroke prophylaxis in AF. Despite adherence to AC, a significant number of patients are still subtherapeutic. In addition to this, several patients are ineligible for AC because of various reasons, including but not limited to high bleeding risk, ongoing bleeding, and non-compliance. These challenges associated with AC led to efforts looking at mechanical isolation of the LAA. Various endocardial and epicardial devices have been tried for mechanical isolation of the LAA, with variable success. The WATCHMANt (Boston Scientific, Maple Grove, MN) is the first endocardial device that received FDA approval as an alternative for warfarin for stroke prophylaxis in AF. The WATCHMANt (Boston Scientific) is not approved for AC-ineligible patients. The LARIAT s (SentreHEART, Inc., Redwood City, CA) is an epicardially deployed device that has been proposed for AC-ineligible patients. Although not FDA approved, its safety and efficacy had been established in large prospective registries. The current review examines the current literature on AC and LAA exclusion devices in a comparative fashion. The protean effects of LARIAT s (SentreHEART, Inc.) on rhythm and neurohormonal control are also reviewed. We conclude that LAA exclusion devices are an excellent alternative to AC for stroke prophylaxis in AC-eligible (WATCHMANt, Boston Scientific) and ineligible patients (LARIAT s , SentreHEART).KEYWORDS. left atrial appendage closure, novel oral anticoagulants, stroke, warfarin.