RATIONALE: This study analyses, within Italian clinical practice, the epidemiology, healthcare resource utilization, and direct costs for the National Health Service (NHS) of patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM). METHODS: From the ReS healthcare administrative database (4.6 million beneficiaries in 2022), patients with ATTR-CM were identified (2014-2022) through dispensation of tafamidis 61 mg or diagnosis of heart failure/arrhythmic cardiomyopathy with a compatible diagnostic work-up. Prevalence, clinical characteristics, mortality, treatments, healthcare resource utilization, and costs were estimated during the 1-year follow-up. RESULTS: 867 patients with ATTR-CM were identified in 2022 (male: 63%; mean age: 73 years; ≥3 comorbidities: 88.6%). During follow-up, 13% of patients died; 46% were hospitalized under ordinary care; 46.8% visited the emergency department; 96.5% received outpatient specialist care. Tafamidis 61 mg was dispensed to 49 patients (5.7%). The average annual cost per patient, borne by the NHS, was €17,284 (59.7% attributable to pharmaceuticals). CONCLUSIONS: The impact of ATTR-CM on the NHS is considerable, due to advanced patient age, multimorbidity, polypharmacy, and frequent hospitalizations, both related and unrelated to ATTR-CM.