OBJECTIVES: LAM is the standard therapy for CHB in Mexico. In well-controlled trials, ADV has shown to be more efficacious, giving the opportunity for a gain in quantity and quality of life but with a greater acquisition cost than LAM. The most cost-effective alternative must be established. METHODS: We calculated life-time direct medical costs of treatment for CHB, including progression of disease either to cirrhosis (compensated and decompensated) or to hepatocellular cancer, under the public provider of health services in Mexico. The resource use for the standard patient in all stages of CHB was obtained by Expert Panel. Official lists of unitary costs were used. The competing strategies were 100mg LAM and 10mg ADV, both taken once daily. We evaluated a hypothetical cohort of 100,000 patients 30 years of age using a Markov model with 45 annually cycles to obtain expected costs, progression of the disease and survival for each alternative. Health-state utilities were obtained from a systematic review. RESULTS: Results were stratified by HBeAg statuts. Compared with LAM, the monotherapy with ADV in HBeAg+ patients represents a gain in almost 5 years of life or 2.20 Quality-adjusted-life-years (QALYs). HBeAg- patients treated with ADV expect a gain in almost 10 years of life or 4.90 QALYs compared with those treated with LAM. Expected life-time direct medical costs for patients treated with ADV were US$32.806 in HBeAg+ patients and US$26.645 in HBeAg- patients. In people treated with LAM, costs for CHB were US$37.573 and US$36.475 for HBeAg+ and HBeAg-, respectively. CONCLUSION: This study showed the clinical and economic benefits of treating CHB patients with ADV. Patients treated with ADV expect a gain in quantity and quality of life. Since monotherapy with ADV is both more effective and less costly strategy than LAM, it becomes the dominant option for CHB in Mexico.