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Spectacled caimans (Caiman crocodilus Linnaeus, 1758) are established invaders in the United States, Cuba, and San Andres Island, Colombia. They have been established in South Florida since the 1970s and are found primarily within Comprehensive Everglades Restoration Plan (CERP) projects. These projects provide suitable habitat and may provide dispersal pathways via water management activities. Caiman presence in these areas directly conflicts with the CERP’s goals, and as a generalist species with a broad diet, they can impact biological resources. Past removal efforts failed to extirpate caimans, but their efficacy has not been well evaluated. We addressed caimans via removal surveys during 2012–2021 with the goal of evaluating extirpation or maximum species control within South Florida’s CERP projects. Documented opportunistic removals for this study began in December 2012, and systematic efforts have been ongoing since October 2017. We evaluated efficacy of caiman removals by analyzing 10 years of opportunistic and systematic survey data, plus associated removal data, along 11 survey routes during 2012–2021. We also conducted necropsies to collect biological information which could be used to improve removal efforts. We removed 251 caimans during 2012 to 2021, and the rate of caiman removals per year increased from 5 animals during 2012 to a peak of 47 animals during 2020. Necropsies revealed reproductive information (nesting/hatching timelines) that we applied to improve our removal rates. Caiman encounter rates declined from a peak of 1.55 ± 0.66 caiman/hr and 0.72 ± 0.38 caiman/km during 2013 to a low of 0.18 ± 0.09 caiman/hr and 0.03 ± 0.02 caiman/km during 2020 and slightly increased during 2020–2021, likely because of a change in search effort. We evaluated and discussed the potential for extirpating caiman from CERP projects and provide a data-driven prescription for removal efforts. [ABSTRACT FROM AUTHOR]