OBJECTIVES CHB subjects have a higher risk of death due to complications, which contribute to the highest expenses in health. This study aims to evaluate whether long-term entecavir therapy is cost effective by suppression of viral replication to undetectable levels when compared to lamivudine. METHODS A decision analysis model was developed, using the following endpoints: cost per patient with undetectable viral load and cost per QALY gained. The analysis was conducted from the perspective of the Brazilian Public Health System (SUS). Adjusted relative risks on the relationship between HBV-DNA viral load (VL) categories and clinical events were estimated from a large scale epidemiology study (REVEAL-HBV Study) cohort. These results were applied to HBeAg+ and HBeAg- patients enrolled in a phase III trial , in which HBV DNA values were measured after 48 weeks of therapy with either entecavir or lamivudine monotherapy, to project subsequent clinical events (CC, HCC, DC). RESULTS ETV, in comparison with LVD, presented lower cost per patient reaching undetectable viral load (eg., for HBeAg positive: R$-7938 and HBeAg negative: R$-5420) , lower cost per life-year saved (eg., for HBeAg positive: R$-2626 and HBeAg negative: R$-1424) and lower cost per QALY gained (eg., for HBeAg positive: R$2,930 and HBeAg negative: R$1,590), being costs-savings for the SUS. CONCLUSIONS These results support the conclusion that long term ETV therapy remains highly cost effective either in HBeAg+ and HBeAg- patients compared with lamivudine due to less numbers of chronic complication of the disease leading to a cost saving scenario for SUS.