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Abstract Context Feral cats, Felis catus, have caused the decline and extinction of many species worldwide, particularly on islands and in Australia where native species are generally naïve to the threat of this introduced predator. Effectively reducing cat populations to protect wildlife is challenging because cats have a cryptic nature, high reproductive rate and strong reinvasion ability. Aims We experimentally tested the response of feral cats and their native prey to an Eradicat® poison baiting program at a conservation reserve. Methods Baits were distributed by hand along roads and tracks every 50 m (~10 baits km−2). We used camera traps to monitor the response of cats to baiting using a repeated before–after, control–impact design over 6 years. We also measured introduced rabbit, Oryctolagus cuniculus, activity by using sand pads and small mammal and reptile captures by using pitfall trapping. Key results Dynamic occupancy modelling showed only modest effects of baiting on cats in 2 of 6 years, with occupancy in the baited area decreasing from 54% to 19% in 2014 (–35%) and from 89% to 63% in 2017 (–26%). Baiting effectiveness was not related to antecedent rainfall or prey availability. Bait availability was reduced by non-target interference; 73% of 41 monitored baits were removed by non-target species. We found no evidence for persistent changes in small mammal or reptile capture rates in the baited area relative to the unbaited area over the life of the project. Conclusions Relatively low baiting density and non-target interference with baits are likely to have reduced baiting efficacy. Further testing and refinement of ground baiting is needed, including trialling higher baiting densities and/or frequencies. Implications We highlight key areas for future research that should benefit feral cat management not only in Australia, but also on the many islands worldwide where cats threaten native wildlife.