Abstract Objective The aim of this study was to assess the prognostic value of different nutritional screening tools in patients undergoing cardiopulmonary bypass with regard to an adverse clinical course. Methods This prospective cohort study analyzed 894 adult patients who underwent cardiopulmonary bypass. Patients were screened using four nutritional screening tools: Nutritional Risk Screening 2002 (NRS-2002), the Malnutrition Universal Screening Tool (MUST), the Mini-Nutritional Assessment (MNA), and the Short Nutritional Assessment Questionnaire (SNAQ). Nutritional status was assessed using the Subjective Global Assessment. In-hospital mortality, postoperative complications, length of stay in the intensive care unit, and length of hospitalization were analyzed. Results The sensitivities of the SNAQ, MUST, and NRS-2002 to detect the malnutrition confirmed by the Subjective Global Assessment were 91.5%, 97.9%, and 38.3%, respectively, and the MNA showed a sensitivity of 81.8% for the elderly. Malnutrition detected by the SNAQ, MUST, and NRS-2002 was associated with postoperative complications (odds ratios [ORs] 1.75, 1.98, and 1.82, respectively) and a stay in the intensive care unit longer than 2 d (ORs 1.46, 1.56, and 2.8). Malnutrition as detected by the SNAQ and MUST was also associated with prolonged hospitalization (ORs 1.49 and 1.59). According to multivariate logistic regression analysis, postoperative complications were independently predicted by the European System for Cardiac Operative Risk Evaluation (OR 1.1, P < 0.0001), cardiopulmonary bypass time (OR 1.01, P < 0.0001), and malnutrition identified by the MUST (OR 1.2, P = 0.01). Conclusion The MUST independently predicts postoperative complications. The SNAQ and MUST have comparable accuracy in detecting malnutrition. Whether preoperative nutritional therapy would improve the outcome in malnourished patients needs to be studied.