The purpose of this paper is to determine the cost-effectiveness of vaccinating inmates against hepatitis B. From the prison perspective, vaccinating inmates at intake is not cost-saving. It could be economically beneficial when the cost of a vaccine dose is <US dollars 30 per dose, or there is no prevalence of infection upon intake, or the costs of treating acute or chronic disease are about 70% higher than baseline costs, or the incidence of infection during and after custody were >1.6 and 50%, respectively. The health care system realizes net savings even when there is no incidence in prison, or there is no cost of chronic liver disease, or when only one dose of vaccine is administered. Thus, while prisons might not have economic incentives to implement hepatitis B vaccination programs, the health care system would benefit from allocating resources to them.