OBJECTIVES: To evaluate the cost-effectiveness of entecavir(ETV) vs.lamivudine(LVD) in the treatment of nucleoside-naive CHB patients and vs. adefovir(ADV) in LVD refractory CHB patients in Turkey. METHODS: A decision-tree model compared cost and effect of treating CHB patients over a 10-year period. Treatment effect in terms of viral load(VL) reduction predicted risk of long-term liver complications. Two CHB patient populations were studied: 1) nucleoside-naïve patients treated for 2 years with ETV(0,5mg/day) vs. LVD(100mg/day) and ADV as salvage therapy in case of LVD resistance; and 2)LVD- refractory patients treated for 10 years with ETV(1mg/day) vs. ADV(10mg/day). Effectiveness was measured as LYS and QALY. Efficacy data were obtained from pivotal trials, relative-risk estimations were derived from the R.E.V.E.A.L.-HBV Study cohort. A Turkish health care payer perspective was considered and a 3% discount rate was used for costs and outcomes. RESULTS: In the cohort of HBeAg(+/-) CHB patients, net incremental drug cost of ETV was higher compared to LVD. However, ETV was associated with a lower projected number of liver events (-73 and -55CC events, -43 and -33HCC events respectively, -8DC events in each cohort) compared with LVD. In nucleoside-naïve HBeAg(+) patients, ETV compared with LVD and ADV as salvage therapy gained 0.82LYS and 0.68QALYs at an incremental cost of 5384TL(6571TL/LYS and 7865TL/QALY). In nucleoside-naïve HBeAg(-) patients, ETV generated 0.66LYS and 0.55QALY at an incremental cost of 7257TL(11039TL/LYS and 13,203TL/QALY). In LVD-refractory patients, ETV generated 0.48LYS and 0.40QALY with a saving of 14,117TL(-29,416TL/LYS and -35,178TL/QALY). CONCLUSIONS: This cost-effectiveness analysis suggests that in the Turkish health care system, ETV is a cost-effective treatment option compared with LVD in the treatment of naïve CHB patients. In LVD refractory patients, ETV  is a cost-saving treatment option relative to LVD with ADV as salvage therapy. Cost-benefits with ETV therapy are explained lower overall CHB treatment costs due to slower disease progression rate and avoidance of resistance associated with LVD.