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While newer heater-cooler technologies using ethylene glycol-based (GB) solutions during cardiothoracic surgery have become commercially available, there is a paucity of clinical data describing their effectiveness during cardiopulmonary bypass (CPB) support. This analysis aimed to compare clinical characteristics and procedural outcomes using water-based (WB) and GB heater-cooler systems.A retrospective analysis was performed on consecutive adult patients undergoing CPB from June to October 2022 comparing WB or GB groups. The primary outcome was a composite of operative death or major morbidity. Secondary endpoints included transfusion requirements on CPB, patient cooling and warming rates, and vasoactive-inotropic scores (VIS) at case completion. P-control charts were used to monitor the weekly incidence of the composite outcome. A sub-analysis was performed to evaluate the primary outcome for cardiac surgery cases indexed by the Society of Thoracic Surgeons (STS).There were 167 patients included for analysis; 87 (52.1%) underwent CPB with a WB system and 80 (47.9%) with a GB system. GB procedure subjects were younger (p = .01), experienced longer CPB times (p = .034), and were more likely to receive thoracic transplant or aortic surgery (p = 0.015). The composite outcome of operative mortality or major morbidity occurred in 29.9% and 24% of the WB and GB groups, respectively (p = .372). P-control charts indicated a weekly mean incidence of 30% during WB practice, which decreased to 24% with GB practice. Among 106 STS-indexed cardiac surgery cases, mean composite outcome incidence decreased from 19% to 6% following our GB transition. Additionally, cooling, and warming rates indexed to patient BSA and VIS at case completion were not significantly different.Our analysis demonstrated a safe transition from WB to GB heater-cooler technologies in our practice. This early analysis suggests that GB heater coolers may be safely adopted to mitigate the risks of nontuberculous mycobacterium infections for cardiac surgical patients. [ABSTRACT FROM AUTHOR]