SUMMARYWe investigated the cost-effectiveness of different influenza control strategies in a school setting in Taiwan. A susceptible-exposure-infected-recovery (SEIR) model was used to simulate influenza transmission and we used a basic reproduction number (R0)–asymptomatic proportion (θ) control scheme to develop a cost-effectiveness model. Based on our dynamic transmission model and economic evaluation, this study indicated that the optimal cost-effective strategy for all modelling scenarios was a combination of natural ventilation and respiratory masking. The estimated costs were US$10/year per person in winter for one kindergarten student. The cost for hand washing was estimated to be US$32/year per person, which was much lower than that of isolation (US$55/year per person) and vaccination (US$86/year per person) in containing seasonal influenza. Transmission model-based, cost-effectiveness analysis can be a useful tool for providing insight into the impacts of economic factors and health benefits on certain strategies for controlling seasonal influenza.