Elderly people are at great risk for influenza-related serious complications. However, influenza vaccine-induced antibodies are believed to decline more rapidly in the elderly. This study was designed to evaluate the long-term and cross-reactive immunogenicity among those aged ≥65 years for two seasonal trivalent influenza vaccines during the 2009–2010 influenza season. One vaccine had the MF59 adjuvant, while the other did not contain an adjuvant. Serum hemagglutinin inhibition (HI) titers were determined pre-vaccination and at 1 and 6 months post-vaccination. Of the 100 subjects, 95 (95%) were followed-up for 1 month after vaccination, and 76 (76%) were followed-up for 6 months after vaccination. Both vaccines met the European Medicines Agency (EMA) criteria 1 month after vaccination. However, seroprotection for influenza B was not satisfactory, with a rate of 55.3% for the MF59 adjuvant vaccine and 47.9% for the vaccine without adjuvant. At 6 months post-vaccination, the MF59-adjuvanted vaccine showed a higher seroprotection rate than the unadjuvanted vaccine. At this point, the MF59-adjuvanated vaccine still met the criteria of EMA for A/H1N1 (62.5% vs. 55.5%, P = 0.64) and A/H3N2 (72.5% vs. 47.2%, P = 0.04). Both vaccines showed excellent cross-reactive immunogenicity for influenza A/Solomon Island/3/2006 (H1N1) and A/Wisconsin/67/2005 (H3N2), without significant differences. In comparison, cross-reactive immunogenicity was not remarkable for the A/California/7/2009 (H1N1) and A/New Caledonia/20/1999 (H1N1) strains, which have a greater antigenic distance. In conclusion, the MF59-adjuvanted influenza vaccine showed superior long-term immunogenicity in the elderly compared to the unadjuvanted vaccine. However, cross-reactive immunogenicity was not remarkably enhanced with the MF59 adjuvant. J. Med. Virol. 85:1591–1597, 2013. © 2013 Wiley Periodicals, Inc.