Although valuable and effective in decreasing disease burden, influenza vaccination has low rates of efficacy, especially in those at most risk. Studies have shown that acute exercise can improve vaccine responses, most consistently with weaker antigens. Here we examined the effect of resistance exercise on the acute and longer-term responses to influenza vaccination among healthy older adults. Forty-six participants (47.8% male, mean 73.4 ± 6.6 years) were randomised to perform one 45-min moderate-intensity resistance exercise session or sit quietly prior to the receipt of influenza vaccination. Acute exercise reduced vaccine reactions but had no effect on either antibody responses or development of influenza-like symptoms during six months of follow-up. Psychosocial and behavioural characteristics were examined for potential associations with the responses to vaccination. Participants (n = 36) vaccinated in the previous year had higher baseline antibody titres but not follow-up titres nor more frequent experience of influenza-like symptoms over 6 months compared to those unvaccinated in the previous year. These findings provide further support for the ability of acute exercise to reduce vaccine reactions and suggest risk factors for vaccine responses for future exploration.