Background Patients with heart failure (HF) have lower initial antibody responses to the influenza vaccine compared with healthy individuals. Whether antibody titers wane faster in this population remains unknown. Methods and Results We studied 62 HF patients (18 ischemic, 44 idiopathic) and 40 healthy control subjects (HC) during the 2006-2007 and 2007-2008 influenza seasons. Antibody titers were measured before and 2-4 weeks and 11-12 months after vaccination. Serum antibody production was measured by hemagglutination inhibition assay, and antibody titers to individual vaccine viral strains between the HF and HC groups were compared after the influenza season to measure persistence of antibody response. All participants demonstrated early antibody seroprotection (titers 40 hemmaglutination inhibition units to 1 strain). Although antibody titers waned over time in both groups, titers to A/H3N2 and A/H1N1 strains decreased more in HF than in HC participants (P =.004 and P =.04, respectively). Titers to the B-type strain decreased to below seroprotective levels in both groups. Conclusions Antibody titers to influenza A vaccine strains wane to below seroprotective levels in HF patients compared with HC, despite similar rates of initial seroprotection and seroconversion. These findings suggest that HF patients may remain at increased risk for influenza infection despite annual vaccination.