- The next influenza pandemic is expected to spread rapidly, causing worldwide morbidity, mortality and economic disruption. Effective vaccines are pivotal to thwart the spread of a pandemic virus and to prevent illness and death. However, the global potential vaccine supply is several billion doses short of the necessary amount. Health authorities worldwide face two main strategies to afford a reasonable chance for utilizing vaccines during pandemic preemptive stockpiling of vaccines against circulating avian H5N1 strains, or signing an advanced purchase agreement for vaccines with the vaccine manufacturers. Both options are costly, and associated with many unknown influencing factors. We present a mathematical model for the comparison of these two vaccine purchase strategies (advanced purchase agreement vs. pre-pandemic avian H5N1 vaccine stockpiling) in economical terms We modeled each strategy's cost, impact on reduction in morbidity and mortality compared with a non-intervention base-case scenario, adjusted the benefits to an annual probability of a pandemic as low as 1%, and calculated the relevant cost-benefit ratio. The impact of vaccination on disease spread was assessed according to a systematic review of published dynamic models. The model showed advanced purchase agreement to be cost saving, with a cost-benefit ratio of 1.75-3.54, depending on the assumed R0. The ratio proved relatively robust in extensive sensitivity analyses. Stockpiling H5N1 vaccine was not cost saving, with a cost-benefit ratio of 0.18. Current signing of an advance purchase agreement for future (pandemic phase) vaccine supply is a cost-saving strategy and should be pursued.