The study addresses the economic effectiveness of vaccination in the case of highly pathogenic avian influenza (HPAI) outbreaks. The effectiveness is evaluated in a U.S. case study comparing the outbreak costs under the currently recommended HPAI control practice versus one which also includes vaccination. An integrated economic-epidemic partial equilibrium model is used to empirically simulate HPAI outbreaks in three different poultry regions within the State of Texas. The simulation results show that the effectiveness of vaccination depends on flock density in the region and risk aversion preferences of the decision maker. In regions with high flock densities, if the decision maker is less risk averse the currently recommended strategy—which includes depopulation, movement restrictions, and flock testing—is more cost-effective than the same strategy supplemented with vaccination. Addition of vaccination improves cost effectiveness only if the decision maker is highly risk averse or if surveillance, carcass disposal, and cleaning costs are high. In regions with medium and low flock densities, adding vaccination to the currently recommended strategy is not cost-effective except in the case of high surveillance, carcass disposal, and cleaning costs.