Highly pathogenic avian influenza (HPAI) is an extremely transmissible virus that poses a significant threat to the U.S. turkey industry through contagion from migratory birds and results in whole-farm depopulation. To combat the disastrous economic impacts of HPAI, this study examined how biosecurity investments may have economic benefits to producers and the industry. Using data collected from a farm-focused survey of commercial turkey producers, the differences in biosecurity practices between farms affected by HPAI and unaffected farms in 2022 were analyzed. This evaluation aims to understand how effective biosecurity investments were towards reducing the susceptibility of a turkey farm to HPAI and what types of farms were more likely to make those types of investments. Factors associated with lower chances of being infected included having any hens, making any temporary biosecurity investments to the farm since 2015 such as temporary wild bird mitigation, and making specific permanent biosecurity investments such as improving feed bins, vehicle wash stations, and barn ventilation systems. Also, those farms that raised any hens, those that participated in the NPIP, and those without livestock access around turkey barns were more likely to make biosecurity investments. These findings aid in informing producers, integrators, and public policy on how to reduce the spread of HPAI to benefit both the economy and longevity of the poultry industry.