Safety and immunogenicity of the influenza vaccine adjuvanted with MF59 (FLUAD^TM) were compared to those of a non adjuvanted subunit vaccine in elderly subjects during three consecutive influenza seasons. Geometric mean titres and proportions of subjects with either a ≥four-fold increase in antibody titres or with an HI titre ≥128 after immunisation were higher in FLUAD^TM recipients. The adjuvant effect on the magnitude of the responses was most pronounced in subjects with pre-vaccination titres ≤40. Although associated with more frequent mild local reactions, the adjuvanted vaccine was well tolerated. Thus, the addition of MF59 increased the immunogenicity of the subunit influenza vaccine in elderly persons with low pre-vaccination titres, who are at greatest risk of developing severe influenza disease and vaccine failure, without a clinically important increase in reactogenicity.