OBJECTIVES: To demonstrate the efficacy, security and effectiveness of tenofovir disoproxil fumarate (Viread®) in the treatment of patients with chronic hepatitis B (CHB) in Mexico, from the Mexican institutional perspective.  METHODS: We used decision analysis to calculate the cost-effectiveness of 5 competing strategies in CHB treatment, 1) tenofovir DF; 2) Entecavir; 3) Adefovir; 4) Lamivudine; and 5) Peginterferon alfa-2a, from the insititutional perspective. A Markov model was developed over 40 years’ time horizon. The outcome measure was the life years gained (LY). Direct health care cost where used and the discount rate was of 5% for cost and life years, also incremental cost effectiveness ratio (ICER), sensitivity analyses and probabilistic sensitivity analyses were performed. RESULTS: Tenofovir DF had more effectiveness and less cost in the treatment of CHB; in the Markov model tenofovir DF had the highest life years gained compared with all other therapies under evaluation. Tenofovir DF had 15.49LY with a cost of $363,314.84, Entecavir had 15.37LF with a cost of $435,849.99, Adefovir had 14.89LY with a cost of $487,457.55, Lamivudina had 13.84LY with a cost of $498,603.87 and Peginterferon alfa-2a had 13.56LY with a cost of $406,795.25, hence all the therapies had an ICER dominated by tenofovir DF in all the scenarios. The sensitivity analyses proved that tenofovir DF was cost effective compared to all other therapies under evaluation in the treatment of CHB patients in Mexico. According to the probabilistic sensitivity analyses, the likelihood of tenofovir DF to be cost effective is 88% under the willingness-to-pay threshold in Mexico.   CONCLUSIONS: There is evidence from the clinical and the cost effectiveness study that the use of tenofovir DF in the treatment of patients with CHB is cost effective, and must be considered as first option in the treatment of patients with CHB diagnosis in Mexico.