OBJECTIVES: The aim of this study is to analyze the cost-effectiveness over 6-year duration of first line telbivudine and lamivudine treatment in HBeAg-positive chronic hepatitis B patients with low viral load at baseline in line with the Turkish reimbursement guideline for oral CHB therapies. METHODS: Using a decision analytical model, cost-effectiveness of telbivudine was evaluated versus lamivudine in first-line use for HBeAg-positive patients with baseline HBV DNA levels <9 log10 copies/mL in Turkish healthcare setting from National Payer’s perspective in accordance with the local reimbursement guideline for oral CHB treatments based on roadmap concept. Primary measure of effectiveness was undetectable HBV DNA level by polymerase chain reaction (PCR) assay at model duration, while costs included only cost of oral CHB drugs incurred by the Payer. Probabilities of PCR negativity and resistance rates used in the model are derived from telbivudine’s head-to-head study versus lamivudine subgroup analyses outcomes for week 24 and 104; and from respective pivotal clinical studies for second line treatments. RESULTS: In the CE model, total oral CHB treatment cost per HBeAg-positive patient treated with lamivudine and telbivudine arm over 6 years was estimated to be 12,873€ and 11,435€ respectively. Percentage of patients remaining on lamivudine at model duration was 23%, while 50% on telbivudine. The average cost-effectiveness ratio, cost per successfully treated HBeAg-positive patient at year 6, was calculated as 15,362€ for the lamivudine arm and 13,053€ for the telbivudine arm (difference is 2,309€), and the incremental cost-effectiveness ratio was -37,859€. CONCLUSIONS: First line CHB treatment with telbivudine in HBeAg-positive patients has been demonstrated as a dominant cost-effective option than lamivudine in the Turkish healthcare setting. Although telbivudine has higher reimbursement price, it has been offset by superior efficacy compared to lamivudine in positive patients with baseline serum HBV DNA levels <9 log10 copies/mL and less need for more costly second line treatments.