OBJECTIVES: To estimate the long-time cost-effectiveness of Left Atrial Appendage (LAA) occlusion device for preventing stroke in a hypothetical cohort of 65-year-old patients with atrial fibrillation (AF). METHODS: A decision analytic model was used to perform a cost-effectiveness analysis comparing LAA occlusion device and 5 alternative anticoagulant therapies from a health care provider perspective. Treatment strategies for AF are included Aspirin, dual therapy with Aspirin and Clopidogrel, Warfarin, Dabigatran 150mg or 110mg, and LAA occlusion device. The parameters including rate of adverse events, utility, and costs were derived from the ACTIVE trial, RE-LY trial, PROTECT trial, and published references in our model. Outcomes are quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs). Costs and QALYs were discounted at an annual rate of 3%. One way sensitivity varied by the CHADS2score and probabilistic sensitivity analyses (PSAs) were conducted to assess parameter uncertainty. RESULTS: Compared with Aspirin, LAA occlusion device, Warfarin, Dabigatran 150mg and 110mg were cost-effective. The ICERs were US$975 per QALY with LAA occlusion device, US$4,982 per QALY with Warfarin, US $10,672 per QALY with Dabigatran 150mg, US$10,972 per QALY with Dabigatran 110mg. When using Warfarin as a comparator, LAA occlusion device is less costly and more effective, Dabigatran 150mg cost US$28,556 per QALY, and Dabigatran 110mg cost UD$37,328 per QALY. For patient with CHADS2 score of 0, 1, 2, 3, or ³a4, the ICREs of LAA occlusion device over Aspirin were US$1,257 per QALY, US$1,104 per QALY, US$894 per QALY, US$626 per QALY, US$518 per QALY, respectively. LAA occlusion device was cost-effective over 95% of the Monte Carlo simulation using a cost-effectiveness threshold of US$50,000 per QALY. CONCLUSIONS: The LAA occlusion device is considered cost-effective compared with Aspirin, Warfarin, Dabigatran 150mg or 110mg in AF patients.