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During cardiopulmonary bypass (CPB), supranormal concentrations of oxygen are routinely administered with the intention to prevent cellular hypoxia. However, hyperoxemia may have adverse effects on patient outcome. Oxygen settings are based on the perfusionist’s individual work experience rather than profound recommendations and studies analyzing the effect of oxygen levels are in need of methodological improvement. We aimed to advance perfusion technique by developing and clinically applying a formula for tailored oxygen therapy in CPB.