OBJECTIVES: It has been suggested that radiofrequency catheter ablation could take priority over antiarrhythmic drugs as first-line treatment of paroxysmal AF, due to better efficiency, and fewer serious side effects. The objective of this study was to evaluate the cost-effectiveness of treating paroxysmal atrial fibrillation with radiofrequency catheter ablation as first-line treatment. METHODS: A decision-analytic Markov model was developed to study long-term effects and costs of catheter ablation compared to antiarrhythmic drugs as first-line treatment.  RESULTS: Small, positive clinical effects were found in the overall population, a gain of an average 0.06 quality-adjusted life years (QALYs) to an incremental cost of €3033, resulting in an incremental cost-effectiveness ratio of €50 570/QALY. However, the incremental cost-effectiveness ratio of a 45-year-old patient was approximately €3434/QALY, while a 65-year-old costs €108 937 per QALY. CONCLUSIONS: Radio-frequency catheter ablation as first-line treatment is a cost-effective strategy for younger patients with paroxysmal atrial fibrillation. However, the cost-effectiveness of using catheter ablation as first-line therapy in older patients is uncertain, and in most of these cases antiarrhythmic drug therapy should be attempted before catheter ablation.