Background: Acquired immune deficiency syndrome (AIDS) is one of the greatest social health problems in many communities in the twenty-first century. Methadone maintenance treatment (MMT) could decrease HIV infection among injection drug users (IDU). The main aim of this paper was to determine the cost-effectiveness of the governmental MMT program to prevent human immunodeficiency virus (HIV) infection among IDU.Methods: This analytical study was performed through a before-after assessment during a one-year period. Using census sampling, 251 IDU referred to the public MMT program of Kerman, Iran, were selected. The expenditures of MMT centers were calculated in the view of government (public sector). The cost-effectiveness was calculated using TreeAge software.Findings: MMT centers averted 86 new cases of HIV infection. The total cost of centers was US$471 per client in the year. The share of IDU from current expenditures was 35% and from capital expenditures was 32%. Also, methadone per capita for each person who injected drug was US$514. Per capita expenditure of HIV drug treatment was estimated US$8535 per year. Incremental cost effectiveness ratio (ICER) was US$2856 per year, which means governmental MMT program is cost-effective according to the World Health Organization (WHO) criteria.Conclusion: MMT centers are cost-effective in preventing HIV infection and the access to this program should be facilitated for IDU.