To perform a cost-effectiveness analysis of the introduction of the varicella vaccine in the National Immunization Program of Colombia. A decision analysis model was built to follow two cohorts from birth. One cohort had vaccination, and the other did not. The time horizon was 30 years. The perspective was from the third payer. A micro-costing assessment of varicella in Colombia was undertaken. All costs were expressed in 2008 dollars of December 31. Incremental cost-effectiveness ratio (ICER) was the main outcome measure. A discount rate for health benefits and costs of 3% was used. A sensitivity analysis was made to assess assumptions uncertainty. Vaccination would avoid 9,415,444 consultations, 17,576 hospitalizations, and 1,144 varicella deaths. Cost per Life-Year Gained (LYG) was US$2,527/LYG. From the third payer perspective in Colombia, varicella costs without vaccination would be US$88 millions, and with vaccination US$35 million. The sensitivity analysis shows that the vaccination strategy is not cost-effective if vaccination cost per dose is higher than US$15.6. In the case of a booster dose every ten years, the vaccination would not be cost-effective if vaccination cost per dose is higher than US$9.8. Varicella vaccination is highly cost-effective according to World Health Organization criteria (less than per capita gross domestic product). The authors recommend, weighting the budget impact, the implementation of the varicella vaccine in Colombia.