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The Gambian giant pouched rat (Cricetomys gambianus) is a large rodent that has established a breeding population in the Florida Keys. Should it successfully disperse to mainland Florida, it could continue spreading through much of North America where significant negative ecological and agricultural consequences could result. We rapidly developed the information for implementing an efficient and successful eradication program before dispersal to the mainland occurs. This included development of monitoring and indexing methods and their application to define the animal’s range, the development of baits attractive to Gambian giant pouched rats, efficacy testing of toxicants, and development of bait-delivery devices that exclude native animals. Gambian giant pouched rats appeared confined to the western two-thirds of Grassy Key, but have dispersed across a soil-filled causeway west to Crawl Key. We identified preferred habitat characteristics and potential dispersal pathways. We developed photographic and tracking tile methods for detecting and indexing Gambian giant pouched rats, both of which work well in the face of high densities of non-target species. We identified a commercial anticoagulant bait and we developed a zinc phosphide (an acute toxicant) bait matrix that were well accepted and effective for controlling Gambian giant pouched rats. We also developed a bait station for delivering toxic bait to Gambian giant pouched rats without risk to native species. We consider that the criteria are met for a successful eradication to commence.