The aim of this study was to discriminate between primary and secondary vaccine failure in children with mumps using IgG avidity testing. Thirty-nine serum samples from children with mumps, confirmed by specific IgM, were studied. The patients were grouped according to their immunization status. The secondary immune response was defined by IgG with an avidity index >32%. A secondary response in infected children previously immunized was considered as a secondary vaccine failure. Vaccinated children presented higher IgG titers and IgG avidity than unvaccinated children. The proportion of secondary immune responses in unvaccinated patients was lower than that obtained in previously vaccinated infected patients. Avidity testing can be a useful tool to detect secondary vaccine failure in mumps.