Background: Elderly patients and patients with a poor cardiac function have increased morbidity rates when undergoing cardiac surgery. The aim of this study was to determine whether addition of glycine to a standard preoperative oral immune-enhancing nutrition supplement (OIENS) improves outcome. Glycine-enriched OIENS was compared with 2 formulas: standard OIENS and control. Methods: In this double-blind, 3-armed study, patients scheduled to undergo cardiac surgery with the use of extracorporeal circulation received either the glycine-enriched OIENS (OIENS + glyc, n = 24), standard OIENS (OIENS, n = 25), or control formula (Control, n = 25) for minimally 5 preoperative days. Patients were included if they were aged 70 years or older, had a compromised left ventricular function, or were planned for mitral valve surgery. Main outcome measures were postoperative infectious morbidity, organ function, and postoperative recovery. Results: Infectious morbidity was significantly lower in both treatment groups compared with the control group (p = .02). An infection was diagnosed in 5 and 4 patients in the OIENS + glyc and OIENS groups, respectively, and in 12 control patients. Less supportive therapy was necessary to stabilize circulation in both treatment groups compared with the control group. Median length of hospital stay was 7.0, 6.5, and 8.0 days in the OIENS + glyc, OIENS, and control groups, respectively. Inflammatory responses, as measured by systemic levels of proinflammatory cytokines and surface markers on polymorphonuclear cells, were comparable for all groups. Conclusions: Preoperative OIENS reduces postoperative infectious morbidity and results in a more stable circulation; the addition of glycine does not result in any beneficial effect over standard OIENS.