OBJECTIVES: To analyze the budget impact of two newly registered for Bulgaria antiretroviral medicines tenofovir and emtricitabine for treatment of HIV infection. The point of view is that of health care system and time horizon is one year. METHODS: Budget impact model was created for antiretroviral medicinal therapies for first and second line treatment. Two scenarios were analyzed for highly active antiretroviral therapy (HAART) including 12 medicines combinations for first line and 7 combinations for second line therapy. Health care resources included in the model are medicines, physician consultation first and 11 follow up attendances, 12 clinical, 3 virology and 6 immunology tests. In the model was varied the cost of the medicines therapy and number of patients. RESULTS: Untill June 2009 in Bulgaria are registered 991 HIV positive patients and near 230 of them are on highly active antiretroviral therapy (HAART) – first or second line depending on their virology status. Preliminary results from the budget impact model show that in the first scenario (first line therapy) the combination tenofovir – emtricitabine - efavirenz is cost saving to the healthcare system compared to three of the most effective HAART regimens: AZT/3TC- LPV/r, 3TC/ABC- SQV and TDF-3TC-EFV and saves 141 981,46 Euro, 83461,53 Euro and €2445.99, respectively for one year. The second scenario (second line therapy) is indicated only for certain patients according to their virology status. In this scenario the regimen TDF-FTC-EFV is cost saving to the health care system in comparison with TDF-3TC-EFV and saves €2445.99. CONCLUSIONS: TDF-FTC-EFV is cost saving for the health care system compared to three of the most effective regimens in Bulgaria. The combination is much appropriate as first line HAART.