Quantitative evaluation of control tools for managing invasive species is necessary to assess overall effectiveness and individual variation in treatment susceptibility. Invasive brown treesnakes (Boiga irregularis) on Guam have caused severe ecological and economic effects, pose a risk of accidental introduction to other islands, and are the greatest impediment to the reestablishment of extirpated native fauna. An aerial delivery system for rodent-based toxic baits can reduce brown treesnake abundance and heterogeneity among individuals may influence bait attraction or toxicant susceptibility. Previous baiting trials have either been simulated aerial treatments or relied on slightly different bait capsule compositions and the results of aerial delivery of toxic baits under operational conditions may not be directly comparable. We monitored 30 radio-tagged adult snakes (990–1,265 mm snout-vent length) during an aerial baiting operation in a 55-ha area using transmitters equipped with accelerometers and receivers programed to display a status code indicating mortality if a snake failed to move for >24 hours. We used known-fate models to estimate mortality and evaluate a priori hypotheses explaining differences in mortality based on size, sex, and treatment effects. Eleven radio-tagged snakes died in the aerial baiting treatment period (0.37, 95% CI = 0.21–0.55) and no individuals (0.00, 95% CI = 0.00–0.04) died during the non-treatment period. Our data provide strong evidence for an additive size-based treatment effect on mortality, with smaller adults (0.59, 95% CI = 0.35–0.80) exhibiting higher mortality than larger snakes (0.14, 95% CI = 0.02–0.37) but did not support a sex effect on mortality. The high mortality of snakes during the treatment period indicates that aerial baiting can reduce brown treesnake abundance, but further refinement or use in combination with other removal tools may be necessary to overcome size-based differences in susceptibility and achieve eradication.