Hepatitis D virus (HDV) globally affects nearly 5% of people with chronic hepatitis B virus (HBV) infection. Bulevirtide (BLV) is an HDV/HBV entry inhibitor recently approved for adult patients with chronic hepatitis delta (CHD). In this real-life case report, we describe the virological efficacy, the safety, and the liver function amelioration of one patient with liver compensated cirrhosis with esophageal varices after one-year combo treatment with BLV (2 mg/day in sub-cutaneous injection) and tenofovir disoproxil fumarate (TDF) (245 mg/day). The patient had HDV RNA levels of 9300 IU/mL, 1100 IU/mL, and undetectable at baseline, after three months, and after six months of treatment, respectively. In addition, the model for end-stage liver disease (MELD) score has declined from 11 at baseline to 8 after twelve months of treatment accompanied by alanine aminotransferase (ALT) normalization. Moreover, the treatment significantly improved the liver stiffness measurement (LSM) since a reduction from 34.3 kPa to 24.5 kPa was observed after twelve months of treatment. Furthermore, the treatment was well tolerated, and no dose reduction was needed.