Annual vaccination with influenza vaccines is recommended for protection against influenza in the United States. Past clinical studies and meta-analysis, however, have reported conflicting results on the benefits of annual vaccination. B-cell responses elicited following repeat influenza vaccinations over multiple seasons have not been examined in detail. We analyzed the B-cell and antibody responses in volunteers vaccinated yearly with seasonal trivalent inactivated influenza vaccines (TIV) from 2010 or 2011 to 2014. Statistical analyses were designed to help correct for possible bias due to reduced sample size in the later years of the study. We show that after the second annual vaccination the frequency of vaccine-specific plasmablasts and the binding reactivity of plasmablast-derived polyclonal antibodies (PPAb) are reduced and do not increase in subsequent years. Similar trends are observed with the serum hemagglutination inhibition antibody response after each annual vaccination, as well as the binding reactivity of PPAb for the hemagglutinin of influenza A vaccine components, even with changes in the seasonal vaccine components during the study. Our findings indicate a diminished B-cell response to annually repeated TIV vaccination. These results emphasize the need of developing improved strategies to enhance the immunogenicity and efficacy of annual influenza vaccination.