Objective: Chronic hepatitis B infection has to be treated effectivelydue to its major complications. The aim of this study is to investigateand compare the therapy alternatives treatment costs for hepatitis Be antigen (HBeAg) negative patients with 10-year projection analysisaccording to current reimbursement guideline in Turkey. Materials and Methods: All testing that should be done before thetreatment and during follow-up was determined according to theguideline. Medicinal costs were calculated according to 2014 prices.Cost calculation was performed on 100 hypothetical HBeAg negative, 35 years old patients whose alanine aminotransferase value was>2 X upper limit of the normal laboratory level by taking into consid- eration the risks of resistance seen during the treatment. Switching totenofovir scenario was concocted when resistance to lamivudine andtelbivudine was developed. In pegylated-interferon non-responders,alternative scenarios have been edited and evaluated. Results: The total cost of patients whose treatment was started withpegylated-interferon and switched to lamivudine and tenofovir dueto non-response was found 2,662,504 TL. Treatment cost of patientswhose therapy was passed to tenofovir after initiation with lamivudine or telbivudine was 2,444,175 TL and 3,061,869 TL, respectively.From the beginning of treatment in patients taking entecavir or tenofovir, the 10-year cost of treatment was 3,924,960 TL and 3,884,040TL, respectively. Conclusion: As a result, when assessing the cost of the treatmentof chronic hepatitis B not only medicine box costs, but also drug resistance and laboratory testing costs, should be considered. In ourcountry, on the basis of 10 years cost; pegylated-interferon and lamivudine therapy has been found advantageous in patients with lowviral load, and tenofovir has been found advantageous in patientswith high viral load.