OBJECTIVES: This research aims to explore the intrinsic value of a live-attenuated YF vaccine, its public health impact, and the savings achieved through routine immunization programs, taking Colombia as an example. METHODS:  We used a static cost-effectiveness model to define the health impact and economic benefit of a live-attenuated 17D YF virus strain vaccine used in an infant routine immunization program in Colombia. We considered the epidemiology of the pre-vaccination era in the country to estimate the intrinsic value of such vaccine. Incidence rate of toxic cases was estimated based on cases notified to WHO over a non-epidemic period (1980-2002). An underreporting factor was applied to incidence, as referenced in the literature. Costs related to health care resources was assessed based on WHO-CHOICE. RESULTS: From a payer perspective, routine immunization was on the edge of the very cost-effective threshold with an incremental cost-effectiveness ratio of 9,415 USD per DALY saved. When societal perspective was considered, the vaccine became very cost-effective. Finally, using the 3 times GDP per capita as willingness to pay in Colombia, a YF vaccine would have been cost-effective up to approximately $5 per dose, holding all other parameters constant. The sensitivity analysis highlighted the importance of the underreporting factor and the level of wastage rate as strong value drivers. CONCLUSIONS: The significant uncertainty around the human burden of YF disease has a strong impact on the value of YF vaccines, and therefore on the measurement of the health benefits of vaccination. Taking the more conservative range of underreporting factor and epidemiological parameters, we showed a good “value for money”. In such context, a potential of more than 3 times the current price could have been reached while remaining cost-effective. This study provides insights on the significant discrepancy between the price of the vaccine and its value in an upper middle-income country.