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Cardiothoracic surgery using cardiopulmonary bypass (CPB) triggers an inflammatory state that may be difficult to differentiate from infection. Heparin-binding protein (HBP) is a candidate biomarker for sepsis. As data indicates that HBP normalizes rapidly after cardiothoracic surgery, it may be a suitable early marker of postoperative infection. We therefore aimed to investigate which variables influence postoperative HBP levels and whether elevated HBP concentration is associated with poor surgical outcome. This exploratory, prospective, observational study enrolled 1475 patients undergoing cardiothoracic surgery using CPB, where HBP was measured at ICU arrival.