Aim: We aimed to evaluate the cost-effectiveness of telbivudine versus entecavir with reference to lamivudine by roadmap model. Methods: Decision analysis model was used to study the incremental cost-effectiveness ratios (ICER), i.e. the additional cost (in USD) required to achieve undetectable HBV DNA or HBeAg seroconversion for a patient at 2 years in America and Hong Kong. Entecavir was used as a continuous monotherapy. Lamivudine and telbivudine would be shifted to entecavir if HBV DNA was detectable at month 6 and continued otherwise with drug resistance treated by add-on adefovir. Weighted event rates based on previous reports were estimated for analysis.