Abstract Background Postoperative delirium is a common complication of cardiac surgery associated with higher morbidity, longer hospital stay, risk of cognitive decline, dementia, and mortality. Geriatric patients, patients undergoing cardiac surgery, and intensive care patients are at a high risk of developing postoperative delirium. Gold standard assessments or biomarkers to predict risk factors for delirium, cognitive decline, and dementia in patients undergoing cardiac surgery are not yet available. Methods The FINDERI trial (FINd DElirium RIsk factors) is a prospective, single-center, observational study. In total, 500 patients aged ≥ 50 years undergoing cardiac surgery at the Department of Cardiovascular and Thoracic Surgery of the University of Göttingen Medical Center will be recruited. Our primary aim is to validate a delirium risk assessment in context of cardiac surgery. Our secondary aims are to identify specific preoperative and perioperative factors associated with delirium, cognitive decline, and accelerated dementia after cardiac surgery, and to identify blood-based biomarkers that predict the incidence of postoperative delirium, cognitive decline, or dementia in patients undergoing cardiac surgery. Discussion This prospective, observational study might help to identify patients at high risk for delirium prior to cardiac surgery, and to identify important biological mechanisms by which cardiac surgery is associated with delirium. The predictive value of a delirium screening questionnaire in cardiac surgery might be revealed. Finally, the identification of specific blood biomarkers might help to predict delirium, cognitive decline, and dementia in patients undergoing cardiac surgery. Trial registration: Ethics approval for this study was obtained from the IRB of the University of Göttingen Medical Center. The investigators registered this study in the German Clinical Trials Register (DRKS; https://www.drks.de) (DRKS00025095) on April 19th, 2021.