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Because the brown treesnake (Boiga irregularis) has virtually extirpated the avifauna on Guam and is a threat to other Pacific islands, the development of alternative and efficient control methods is required. Therefore, we performed a large-scale field experiment to determine whether the acetaminophen baits we developed could be used to reduce population levels of brown treesnakes on Guam. Toxic baits were made by inserting 80 mg of acetaminophen into dead neonatal mice, and these mouse baits were used to treat plots. Reference plots were baited with unadulterated baits. We used mark-recapture methods to estimate snake abundance on plots before treatment, monitored bait-take rates on treated plots for 30 days, and used mark-recapture to estimate snake populations post-treatment. Bait-take rates were reduced on treated plots by 83% relative to reference plots after 14 days, when they reached an asymptote. Using a robust design model in program MARK, snakes on reference plots had higher apparent survival rates (x̅ = 0.3505) than those on treated plots (x̅ = 0.0072) for the duration of the study, but estimates were influenced by snake movement between plots. When we accounted for movement using a multistrata model, survival on treated plots was estimated as zero. High mobility of brown treesnakes presents difficulty for complete removal of snakes from large areas, but we conclude that acetaminophen baits may provide an effective and selective management tool for quickly and efficiently reducing populations of brown treesnakes on Guam.