BACKGROUND: The Atrial fibrillation Better Care (ABC) pathway has been proposed to streamline patient management in an integrated, holistic manner. Compliance to ABC resulted in lower incidence of cardiovascular events, but its impact on health-related costs has not been evaluated. METHODS: Exploratory analysis of costs related to cardiovascular events in the ATHERO-AF prospective cohort study including atrial fibrillation patients on vitamin K antagonists. A Diagnosis-Related Group code provided by the Italian Ministry of Health was assigned to each event to estimate the relative cost. The analysis was performed by dividing patients according to ABC pathway components. RESULTS: Overall, 118 cardiovascular events incurred a cost of 1,017,354 euros (1,149,610 USD). The mean total costs were 13,050 (14,747 USD) and 11,218 euros (12,676 USD) for a non-fatal cardiac event or ischaemic stroke, respectively. The cost-saving was 719 euros (813 USD) per patient-year for patients in group A vs non-A, 703 euros (794 USD) for B vs non-B, 480 euros (542 USD) for C vs non-C and 2776 euros (3,137 USD) for ABC vs non-ABC. The cost per event increased with the number of uncontrolled ABC components: 507 euros (573 USD) for 1, 965 euros (1,091 USD) for 2 and 3,431 euros (3,877 USD) for patients not having any of the three components of the ABC. CONCLUSIONS: Management of atrial fibrillation patients according to the ABC pathway was associated with significantly lower health-related costs. Application of the ABC pathway may help reduce healthcare costs related to cardiovascular events in this high-risk patient population.