Annual trivalent influenza vaccines (TIV) containing three influenza strains (A/H1N1, A/H3N2, and one B) have been recommended in Panama since 2006. However, worldwide co-circulation of two distinct B lineages (Victoria and Yamagata) and difficulties in predicting which lineage will predominate in the next season have led to the development of quadrivalent influenza vaccines (QIV) including both B lineages. Our analysis evaluates the public health and economic benefits of using QIV versus TIV in Panama from 2006 to 2013.