OBJECTIVES: Hepatocellular carcinoma (HCC) represents approximately 75% of primary liver cancers and is a major global health problem. For unresectable disease, Trans-Arterial RadioEmbolization (TARE) may be an alternative to sorafenib in intermediate stage patients who failed chemo-embolization or in advanced stage patients with portal vein thrombosis (PVT) with no extra-hepatic spread and good liver function. These treatments are very expensive and in a resource-limited healthcare system, their use should be carefully evaluated. We performed a Budget Impact Analysis (BIA) to simulate an increased utilization of TARE in place of sorafenib for the treatment of intermediate-advanced stage HCC in the Italian National healthcare setting. METHODS: Patient level data were collected at three oncology centres in Italy. A 1-to-1 propensity score matching was performed to obtain two cohorts of patients, treated with TARE or sorafenib, with similar clinical characteristics in terms of Child-Pugh score, number of nodules and PVT. A Markov model was developed to project costs associated to the matched cohorts on a lifetime horizon. Healthcare resource utilization was derived by commonly applied treatment protocols for TARE and sorafenib. Costs were obtained from DRGs reimbursement rates and official tariffs. RESULTS: Considering 1,082 candidates for TARE or sorafenib per year, and scenarios at 1, 3 and 5-years with reasonable increased uses of TARE (30%, 40% and 50%), the BI for the Italian Healthcare Service resulted 31,769,062€, 30,771,546€ and 29,838,449€, respectively. CONCLUSIONS: TARE can be considered a valid and safe treatment option for patients with intermediate-advanced HCC. Our study reveals a potential decrease in the Italian healthcare budget after the diffusion of the new medical device based therapy, thus supporting the economic sustainability at national level of radioembolization in comparison to sorafenib in the relevant population. Further RCTs and real world data will be able to provide additional information to confirm these conclusions.