Bulevirtide (Hepcludex®) is the first drug approved for the treatment of chronic hepatitis D (CHD), unlike the current off-label treatment (PEG-IFN-α), limited in clinical practice and associated with post-treatment relapses. In a hypothetical cohort of CHD patients in Spain, the study aim was to compare the efficiency of bulevirtide with PEG-IFN-α in terms of clinical events avoided and associated cost savings.A validated economic model reflecting the natural history of the disease was used to project lifetime liver complications and costs for two hypothetical cohorts treated with bulevirtide or PEG-IFN-α. The model considered progression to complications such as decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), liver transplantation (LT), and death. The efficacy rates used at 24 and 48 weeks were defined as the combined response rate for bulevirtide and undetectable HDV RNA to PEG-IFN-α. The numbers of clinic events and associated costs were evaluated from the perspective of the National Healthcare System.In a hypothetical cohort of 3882 patients, bulevirtide reduced the numbers of complications events in comparison to PEG-IFN-α (152 DCC, 113 HCC, 11 LT, and 321 deaths over a lifetime). This was associated with a reduction of event-related costs of €11,837,044 (DCC €1,138,059; HCC €1,503,583; LT €7,834,291; and death €1,361,111).In patients with CHD, bulevirtide could prevent a significant number of clinical events compared to PEG-IFN-α and contribute to cost savings through these reduction in liver complications. Further testing for hepatitis D virus is needed so that more patients can benefit from bulevirtide.