OBJECTIVES: Major practice changes require both clinical and economic rationale, especially where a novel device replaces an established pharmaceutical therapy.  Recent studies have reported the clinical benefits of percutaneous left atrial appendage closure (LAAC) for stroke prevention in atrial fibrillation (SPAF) as compared to standard warfarin anticoagulation, but the cost implications of the device-based approach have not yet been demonstrated.  This analysis highlights the ongoing costs of complications associated with a long standing pharmaceutical therapy compared to a device-based approach. METHODS: An Excel-based cost impact model was developed using data from the PROTECT-AF clinical trial which randomized 707 AF patients to either LAAC or warfarin (Holmes 2009). The model captured the costs of complications in AF,  including  strokes, systemic embolism, major extracranial bleeding and complications associated with the LAAC procedure. Costs for stroke included only the acute, direct costs and did not capture the long-term societal costs associated with disability. Germany, which recently recognized the LAAC procedure with a unique DRG code, was the basis for costs, using published DRGs and tariffs associated with procedures, drugs, and care. RESULTS: The high rate of adverse events in the warfarin arm generated €6,414 in medical costs for complications per patient at 5 years, compared to €3,276 for LAAC. These included mean costs of €3,239 for stroke and systemic embolism and €970 for major bleeding in the warfarin arm, compared to €1,551 and €484 respectively for LAAC. The mean annual cost of complications for warfarin was roughly twice that of LAAC, (€1,283 versus €655). CONCLUSIONS: The complication cost differential highlights the need for decision makers to consider the totality of long-term costs and clinical implications of lifetime treatment strategies for SPAF.