The increasing global burden of cardiovascular disease, particularly, in the aging popula-tion, has led to an increase in high-risk cardiac surgical procedures. The current preoper-ative risk stratification scores, such as the European System for Cardiac Operative Risk Evaluation and the Society for Thoracic Surgeons score, have limitations in their predic-tive accuracy and tend to underestimate the mortality risk in higher-risk populations. This systematic review aimed to evaluate the utility of natriuretic peptides, brain natri-uretic peptide (BNP) and its precursor prohormone (N-terminal prohormone BNP), as predictive biomarkers for adverse outcomes after cardiac surgery. A comprehensive search strategy was performed, and 63 studies involving 40,667 patients who underwent major cardiac operations were included for data extraction. Preoperative levels of BNP and N-terminal prohormone BNP seemed to be associated with an increased risk of short -and long-term mortality, postoperative heart failure, kidney injury, and length of inten-sive care unit stay. However, their predictive value for postoperative arrhythmias and myocardial infarction was less established. Our findings suggest that natriuretic peptides may play an important role in risk prediction in patients who underwent cardiac surgery. The addition of these biomarkers to the existing clinical risk stratification strategies may enhance their predictive accuracy. However, this needs to be endorsed by data derived from wide-scale clinical trials. (c) 2023 Elsevier Inc. All rights reserved. (Am J Cardiol 2024;210:16-36)