BACKGROUND Cardiogenic shock requiring mechanical circulatory support is a life-threatening complication of cardiac surgery with cardiopulmonary bypass (CPB). This study aimed to determine the role of myoglobin in predicting the occurrence of postoperative cardiogenic shock requiring mechanical circulatory support within 14 days. METHODS A total of 4610 patients undergoing cardiac surgery with CPB were included and analyzed. Mechanical circulatory support included the form of intra-aortic balloon pump (IABP) and extracorporeal membrane oxygenation (ECMO). Cox regression with a natural cubic spline was used to assess the relationship between postoperative myoglobin levels and the 14-day risk of mechanical circulatory support for cardiogenic shock. RESULTS Of 4610 patients, 279 (6.1%) required mechanical circulatory support within 14 days after surgery. The 14-day risk of using mechanical circulatory support increased with the postoperative peak myoglobin levels. Among the patients who underwent aortic surgery, the threshold myoglobin level measured within 1 day after surgery, associated with an adjusted hazard ratio greater than 1.00 for using mechanical circulatory support within 14 days, was 1568 ng/mL (95% CI, 195 - 6040). Among the patients who underwent non-aortic surgery, the corresponding threshold myoglobin level was 419 ng/mL (95% CI, 180 - 452). CONCLUSIONS Postoperative myoglobin levels are closely related to the 14-day risk of using mechanical circulatory support after cardiac surgery. When postoperative myoglobin exceeds certain thresholds, the 14-day risk of using mechanical circulatory support after surgery starts to increase with the myoglobin level. Myoglobin has potential value in predicting postoperative cardiogenic shock requiring mechanical circulatory support within 14 days after cardiac surgery.