Background: Dengue infection is a major public health problem in Colombia where the largest epidemic with almost 157,000 DF cases and 217 deaths were reported in 2010. However, comprehensive data are scarce, yet essential for decision-making for dengue vaccines introduction. Methods: We are conducting a comprehensive study composed of a passive facility-based surveillance; sero-survey; a healthcare utilization survey; a cost-of-illness (COI) survey; and a willingness-to-pay (WTP) survey to determine the true burden of dengue in the Santa Cruz comuna of Medellin, Colombia. In the surveillance, febrile patients between 1-65 years-of-age are evaluated for dengue infection. Among dengue-confirmed cases, the COI survey estimates the economic burden of disease. For the sero-survey, 2000 randomly selected residents are enrolled to calculate sero-conversion rate. The WTP and the healthcare utilization surveys assess private demand of dengue vaccines and the proportion of febrile cases missed by the passive surveillance. Results: Passive fever surveillance was launched in November, 2011 in Santa Cruz Hospital and three affiliated health centers. It has been a season of low caseload for Colombia with only 26 subjects enrolled until the 31st of Dec. Among 23 samples processed, 3 samples were found to be positive by IgM capture ELISA. As there were none confirmed positive by NS1 rapid test, the COI survey has not begun. In the sero-survey, 61% (n=1191) were found to be positive by IgG indirect ELISA among 1955 samples processed. Prior to the WTP survey, focus group discussions were conducted. It was found that all respondents believe that dengue vaccines should be used and that the government should pay for children's vaccinations and cited price as the most important determinant of demand, followed by efficacy, duration, and side-effects. A reasonable vaccine price was about 20,000 Colombian pesos per dose. Conclusion: The data generated by the DVI with epidemiological, economic, behavioral, market-demand perspectives will be used to build a comprehensive national investment case of dengue vaccine in Colombia, a likely early adopter country of dengue vaccines. The investment case will be used as models for other countries in the respective regions to facilitate accelerated development and introduction of safe and effective dengue vaccines.