OBJECTIVES: A recent randomized controlled trial has demonstrated significant reductions in terms of cardiovascular hospitalizations and deaths with a nurse-led integrated chronic care approach in patients with atrial fibrillation compared to usual care. The objective of the present study is to assess cost-effectiveness of this nurse-led care program versus usual care. METHODS: A cost effectiveness analysis was undertaken alongside the randomized controlled trial in which 712 patients were included at the Maastricht University Medical Centre, Maastricht, The Netherlands, and allocated to nurse-led care or usual care. Nurse-led care implied guideline adherent management, steered by dedicated software and supervised by cardiologists. Usual care was regular outpatient care performed by cardiologists. A cost per lifeyear as well as a cost per QALY analysis was performed, both from a hospital perspective. QALYs were based on scores of the Short Form 36 questionnaire (SF-36), converted to utility scores by extracting the Short Form 6D (SF-6D). All unit prices were supplied by the hospital’s financial department, except for prices for medication, which were taken from the Dutch Pharmacotherapeutic Compass. Results represented the costs and effects for a 12 months follow-up period. RESULTS: The nurse-led care program was associated with slightly more lifeyears and QALYs at a lower cost. Specifically, the nurse-led program contributed to 0.086 QALY gains with a reduced cost of € 1102.77 per patient and a gain of 0.02 life years with a reduced cost of € 731.62 per patient. Therefore, the nurse-led program would be considered dominant. In fact, for all the possible values of willingness to pay for a QALY the nurse-led program is considered to be more likely cost effective than the care as usual. CONCLUSIONS: The cost-effectiveness analysis in the present study demonstrated that a nurse-led integrated care approach is very likely a cost-effective management strategy for patients with atrial fibrillation.