Atrial fibrillation (AF) is associated with a substantial risk of thromboembolic stroke. Although long-term treatment with warfarin or the non-vitamin K oral anticoagulants can reduce this risk, such therapy is underutilized, and safe and consistent long-term treatment can be challenging. Transcatheter left atrial appendage (LAA) closure is an emerging alternative to long-term oral anticoagulation. Long-term follow-up of randomized clinical trials demonstrate that Watchman LAA closure provides significant reductions in hemorrhagic stroke, cardiovascular death, and all-cause mortality compared with continued warfarin therapy. Major bleeding is also reduced compared with continued warfarin therapy once the post-implant pharmacologic regimen is completed. This review summarizes the current dataset for the safety and efficacy of transcatheter LAA closure, and highlights the gaps in evidence and future directions for clinical research.