Annual trivalent influenza vaccines (TIV) containing three influenza strains (A/H1N1, A/H3N2, and one B) have been recommended in Colombia since 2007. 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 Colombia from 2007 to 2014.