Objective. The objective of this study is to evaluate the cost-effectiveness of catheter ablation for rhythm control compared to antiarrhythmic drug (AAD) therapy in patients with atrial fibrillation (AF) who have previously failed on an AAD.Methods. An economic model was developed to compare (1) catheter ablation and (2) AAD (amiodarone 200 mg/day). At the end of the initial 12 month phase of the model, patients are classified as being in normal sinus rhythm or with AF, based on data from a meta-analysis. In the 5-year Markov phase of the model, patients are at risk of ischemic stroke each 3-month model cycle.Results. The model estimated that, compared to the AAD strategy, ablation had $8,539 higher costs, 0.033 fewer strokes, and 0.144 more QALYS over the 5-year time horizon. The incremental cost per QALY of ablation compared to AAD was estimated to be $59,194. The probability of ablation being cost-effective for willingness to pay thresholds of $50,000 and $100,000 was estimated to be 0.89 and 0.90, respectively.Conclusion. Based on current evidence, pulmonary vein ablation for treatment of AF is cost-effective if decision makers willingness to pay for a QALY is $59,194 or higher.