The burden of dengue in Nicaragua has been steadily rising during the last three decades; however, there have been few efforts to quantify the burden (measured in disability-adjusted life years [DALYs]) and cost to society. Using primary data from the Nicaraguan Ministry of Health (MINSA), the total cost and burden of dengue were calculated from 1996 to 2010. Total costs included both direct costs from medical expenditures and prevention activities and indirect costs from lost productivity. The annual disease burden ranged from 99 to 805 DALYs per million, with a majority associated with classic dengue fever. The total cost was estimated to be US$13.5 million/year (range: US$5.1-27.6 million). This analysis can help improve allocation of dengue control resources in Nicaragua and the region. As one of the most comprehensive analyses of its type to date in Nicaragua and Latin America, this study can serve as a model to determine the burden and cost of dengue.