Hepatitis B virus (HBV) infection constitutes a serious global health problem. Nowadays there are divergent data regarding the use of antiviral drugs to treat acute hepatitis B. We present here a case of a 62-year-old man affected by severe acute hepatitis B with progressive worsening of clinical and hepatic function. The patient was treated with entecavir without critical side effects. We observed rapid clinical and laboratory improvements and the disappearance of hepatitis B surface antigen (HBsAg). The treatment with entecavir was protracted until 17(th) week when the antibody anti-HBs appeared. Entecavir should be carefully considered for the treatment of severe acute hepatitis B cases.