AIMS: Combined catheter ablation (CA) and left atrial appendage closure (LAAC) has been proposed for management of symptomatic atrial fibrillation (AF) in patients with high stroke and bleeding risk. We assessed the cost-effectiveness of combined CA and LAAC, compared with CA and standard oral anticoagulation (OAC) in symptomatic AF. METHODS: A Markov model was developed to assess total costs, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) among two post-CA strategies: (1) standard OAC, (2) LAAC (combined CA and LAAC procedure). The base-case used a 10-year time horizon and consisted of a hypothetical cohort of patients aged 65years with symptomatic AF, high thrombotic (CHA2DS2-VASc=3) and bleeding risk (HAS-BLED=3), and planned for AF ablation. Values for transition probabilities, utilities, and costs were derived from the literature. Costs were converted to 2020 USD. Half-cycle correction was applied, and costs and QALYs were discounted at 3% annually. Sensitivity analyses were performed for significant variables and scenario analyses for higher embolic risk. RESULTS: In the base case cohort of 10,000 patients followed for 10years, total costs for the LAAC strategy were $29,027 and for OAC strategy were $27,896. The LAAC strategy was associated with 122 fewer disabling strokes and 203 fewer ICH per 10,000 patients compared with the OAC strategy. The LAAC strategy had an ICER of $11,072 USD/QALY. In sensitivity analyses, although cost-effectiveness was highly dependent on the risk of intracranial hemorrhage in the LAAC strategy and the cost of the combined procedure, LAAC was superior to OAC under the most circumstances. Scenario analyses demonstrated that the combined procedure was more cost-effective in patients with higher stroke risk. CONCLUSION: In symptomatic AF patients with high stroke and bleeding risk who are planned for CA, the combined CA and LAAC procedure may be a cost-effective therapeutic option, and be more beneficial to patients with CHA2DS2-VASc risk score≥3.