Hepatitis B virus (HBV) causes 0.2% of world deaths, especially in developing countries. This does not include deaths of hepatocellular carcinoma (HCC), and hepatic cirrhosis (HC) caused by HBV. To diminish the burden of HBV chronic and acute infection, in an unvaccinated cohort, we proposed a cost-effectiveness analysis to assess the impact of the introduction of HBV vaccine in Colombian adolescents. A Markov model was made for two cohorts (vaccinated and unvaccinated) of people between 15 and 20 years old, who were be followed for 30 years. Vaccination was assumed 97% effective in a three dose scheme, and coverage of 70%. Costs were obtained from a database of Colombian private health insurers. A model to estimate natural history of HBV infection was used, along with data from literature reviews. All costs were 2009 US dollars. Vaccine administration cost plus vaccine price were assumed as US$7. A 3% discount rate was applied to cost and outcomes. A sensitivity analysis was made to assess the uncertainty in the assumptions. Deaths from HBV infection would be 709 in the cohort without vaccination, and 228 in the cohort with vaccination. Life-years gained (LYG) from vaccination with 70% coverage would be 12,266. Total cost in not vaccinated is US$27,840,220; in vaccinated is US$8,936,710. Incremental-Cost-Effectiveness Ratio (ICER) per LYG would be 665 US$/LYG. ICER per avoided death would be 16,957 US$/avoided death. HBV vaccine is highly cost-effective according to World Health Organization criteria (less than per-capita gross domestic product). This is the first study that assessed the adolescent vaccination with HBV in Latin America. The investigators strongly recommend the implementation of this intervention to impact the burden of disease HBV-associated in Colombia.