Game theory is based on the assumption that individuals act according to self-interest and make decisions that maximize their personal payoffs. To test this fundamental assumption, we conducted a survey study in the context of influenza vaccination decisions. Contrary to the assumption of self-interest, we found that altruism plays an important role in vaccination decisions. Nevertheless, altruistic motivation has not yet been considered in epidemiological models, in predictions of vaccination decisions or in the design of vaccination policies. To determine the impact of altruism on the adherence to optimal vaccination policies and on resulting disease burden, we incorporated altruism into a game-theoretic epidemiological model of influenza vaccination. We found that altruism significantly shifted vaccination decisions away from individual self-interest and towards the community optimum, greatly reducing the total cost, morbidity and mortality for the community. Therefore, promoting altruism could be a potential strategy to improve public health outcomes.