Background: Donors positive for hepatitis B core antibody (HBcAb) are an important source of organs in hepatitis B virus (HBV) endemic areas despite the risk of occult infection. We analyzed the long-term outcomes of hepatitis B immunoglobulin in de novo HBV prevention following liver transplantation (LT) using HBcAb-positive grafts. Methods: The prospectively collected data from 2,201 recipients at Seoul National University retrospectively reviewed. A total of 1,458 patients were enrolled. Of the 1,458, 478 (32.8%) grafts were corepositive, 152 (10.4%) of which belonged to HBV surface antigen-negative recipients. During the anhepatic phase, hepatitis B immunoglobulin 4,000 IU was administered intravenously and daily until postoperative day 3. Results: The 152 patients with hepatitis B surface antigen-negative received HBcAb-positive graft. De novo HBV developed in 21 (13.8%) of these recipients. De novo HBV occurred in 1, 11, 0, and 9 of the 4 HBcAb- and hepatitis b surface antibody (anti-HB)-negative, 49 HBcAb-negative and anti-HB-positive, 1 HBcAb-positive and anti-HB-negative, and 98 HBcAb- and anti-HB-positive recipients, respectively. Patients with higher Model for End-stage Liver Disease (MELD) score (23.8 +/- 8.7 vs. 19.5 +/- 9.2) or HBcAbnegative recipients (22.6% vs. 9.1%) had a higher risk of de novo infection. The median follow-up and serum HBV surface antigen-positivity detection time was 69 and 18 months, respectively. The median HBV surface antibody titer was 65.0 IU/L at de novo infection. Nineteen patients of 21 were treated with nucleoside analogs (NAs), and seven of 19 achieved seroconversion. No patient died of de novo HBV infection. Conclusions: With close monitoring of viral serum markers and appropriate initiation of NAs, de novo HBV infection can be prevented and treated appropriately with the hepatitis B immunoglobulin monoprophylaxis protocol.