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Abstract Advances in cardiac surgical operative techniques and myocardial protection have dramatically improved outcomes in the past two decades. An unfortunate and unintended consequence is that 80% of the preventable morbidity and mortality following cardiac surgery now originates outside of the operating room. Our hope is that a renewed emphasis on evidence-based best practice and standardized perioperative care will reduce overall morbidity and mortality and improve patient-centric care. The Perioperative Quality Initiative (POQI) and Enhanced Recovery After Surgery–Cardiac Society (ERAS® Cardiac) have identified significant evidence gaps in perioperative medicine related to cardiac surgery, defined as areas in which there is significant controversy about how best to manage patients. These five areas of focus include patient blood management, goal-directed therapy, acute kidney injury, opioid analgesic reduction, and delirium.