OBJECTIVES: To evaluate the cost-effectiveness of dronedarone for the treatment of atrial fibrillation (AF) compared to current antiarrhythmic drugs (AADs), from a UK NHS perspective. METHODS: A cost-utility analysis was performed, for which an individual patient lifetime discrete event simulation model was constructed. The model predicted a patient’s course for a treatment pathway based on the current National Institute for Health and Clinical Excellence (NICE) AF guidelines and compared treatment with amiodarone, sotalol and Class 1c agents to dronedarone. The model consisted of seven AF-related events; AF recurrence, acute coronary syndromes, stroke, congestive heart failure, treatment discontinuation, AF status change and mortality. Between events patients resided in four health states; normal sinus rhythm, permanent AF with uncontrolled symptoms, permanent AF with controlled symptoms and death. Patient’s baseline event risks were estimated from the non-active comparator arm of the ATHENA trial then adjusted for treatment effects based on a mixed treatment comparison. Cost data were elicited from existing literature and UK reference costs. Quality of life estimates were based on data from the AFTER cohort. Cost-effectiveness was measured in cost per quality adjusted life year (QALY) gained. Costs and QALYs were discounted at 3.5%. One-way and probabilistic sensitivity analyses (PSA) were performed. RESULTS: Dronedarone was shown to be cost-effective with incremental cost effectiveness ratios of £2,406 versus amiodarone, £1,911 versus sotalol and £18,737 versus Class 1c agents. One-way sensitivity analysis showed that treatment effect on mortality was the key driver of cost effectiveness. PSA results estimated that dronedarone was cost-effective at an acceptability threshold of £20,000 on 95% of occasions compared to amiodarone and sotalol and on 60% of occasions compared to Class 1c agents CONCLUSIONS: The results of this analysis demonstrate that in the UK setting dronedarone is a cost-effective treatment of AF compared to current AAD treatment.