Simple SummaryIn the face of a swine health crisis, emerging zoonotic diseases or environmental catastrophe, the mass depopulation of swine may be required to prevent the additional spread of disease and to minimize animal pain or suffering. Due to the increasing risk of global disease outbreaks, the U.S. swine industry needs feasible guidelines in place in preparation for such events. Current American Veterinary Medical Association (AVMA) approved swine depopulation methods can be difficult to implement under field conditions. Emergency depopulation using inhalants such as carbon dioxide (CO2) and nitrogen gas (N2) or the use of aspirated foam agents have been approved and conducted in poultry in the US, but are not approved for use in other livestock. Our findings, using cull sows, demonstrate that although CO2, N2 and aspirated foam combinations successfully killed all the animals, CO2 and aspirated foam did so in the shortest timeframe. In addition, the use of aspirated foam was as effective as CO2 for sow depopulation while having potential operational advantages, such as no use of lethal gases and reduced risk of associated equipment failure.The U.S. swine industry is currently inadequately prepared to counteract the increasing threat of high-consequence diseases. Although approved and preferred depopulation guidelines exist, ventilation shutdown (VSD+) is currently the only method being deployed during a state of emergency to depopulate large swine populations. However, the permitted use of VSD+ during constrained circumstances has been criticized due to raised swine welfare concerns. The objective of this study was to investigate the effectiveness of carbon dioxide gas (CO2), nitrogen gas (N2), compressed air foam (CAF), compressed nitrogen foam (CAF-N2) and aspirated foam (AF) during a 15-min dwell time on adult swine in an emergency depopulation situation. A small-scale trial using 12 sows per depopulation method showed the highest efficiency to induce cessation of movement for AF and CO2 (186.0 ± 48 vs. 202.0 ± 41, s ± SD). The ease of implementation and safety favored AF for further investigation. A large-scale field study using AF to depopulate 134 sows in modified rendering trailers showed a mean fill time of 103.8 s (SD: 5.0 s) and cessation of movement of 128.0 s (SD: 18.6 s) post filling. All sows were confirmed dead post-treatment for both trials. The implementation of AF in modified rendering trailers may allow for a safe and reliable method that allows for the expedient and mobile depopulation of both small and large numbers of sows during an emergency.