Current options for depopulation of adult cattle are limited, have logistic constraints, and may not be practical on a large scale. Aspirated water-based foam has been shown to be successful in depopulating poultry and swine but has yet to be tested in cattle. Water-based foam is advantageous because necessary equipment can be readily available, easy to use, and presents minimal personnel risk. With the use of a modified rendering trailer in a field setting, we evaluated the efficacy of aspirated water-based foam for depopulation of adult cattle. Water-based medium-expansion foam was added to the trailer holding cattle to a depth of approximately 50 cm greater than head height. The study was conducted as a gated design and the initial trial was conducted using 6 anesthetized and 6 conscious animals for verification of the process and followed by four replicates each containing 18 conscious cattle. A total of 84 cattle were used, with a subset (n=52) implanted with subcutaneous bio-loggers that recorded activity and electrocardiograms. Cattle were loaded onto the trailer and three gasoline-powered water pumps delivered foam into the trailer followed by a 15-minute foam dwell period. Average (± SD) time to completely fill the trailer with foam was 84.8 ± 11.0 seconds. No animal vocalizations were heard during foam application or the dwell period, and all cattle were confirmed dead upon removal from the trailer after 15 minutes of immersion. Necropsies of a subset of cattle revealed foam extending to at least the tracheal bifurcation in all cattle and distal to this level in 67% (8/12) animals. Time to cessation of movement, which served as a proxy for loss of consciousness, was 2.5 ± 1.3 minutes and time to cardiac death was 8.5 ± 2.5 minutes as determined by data from animals carrying subcutaneous bio-loggers. The results of this study indicate that water-based foam is a rapid and effective method for depopulation of adult cattle with potential advantages in speed and carcass handling and disposal over current methods.