Aims: To determine efficacy and safety of intravenous hepatitis B immune globulin (Niuliva^®, Grifols) to prevent reinfection in de novo orthotopic liver transplantation. Patients & methods: In a nonrandomized, noncontrolled and Phase III clinical trial, 15 adult patients (12 men) were treated with Niuliva from the anhepatic phase (10,000 IU/daily 1 week postsurgery) up to 6 or 12 months (5000 IU/weekly 1 month; 5000 IU/monthly thereafter). Results: No patients showed reinfection throughout the study. Niuliva was effective in maintaining antibody titers above the thresholds recommended by the European Medicines Agency (EMA) to prevent reinfection (100–150 IU/l). Four serious adverse events were reported in three patients (none related to the study product). There were no seroconversions and no deaths. Conclusion: Long-term, high-dose Niuliva administration was safe and effective to prevent graft reinfection in the tested patients.