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Central and femoral cannulation represent the 2 dominant approaches, each associated with unique anatomical considerations, hemodynamic implications, and perioperative risks. The correct selection of a cannulation strategy should limit the risk of embolic events and associated complications such as vascular injury and stroke. The purpose of this review is to provide a detailed comparison of central and femoral cannulation techniques, with an emphasis on clinical scenarios and outcomes, recent innovations, and state-of-the-art technology. 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