Glutamine is normally an abundant amino acid in the body. It has many important metabolic roles, which may protect or promote tissue integrity and enhance the immune system. Low plasma and tissue levels of glutamine in the critically ill suggest that demand may exceed endogenous supply. A relative deficiency of glutamine could compromise recovery, resulting in prolonged illness and an increase in late mortality, morbidity, and consequently hospital costs. Using a prospective block-randomized, double-blind treatment study design, we tested whether a glutamine-containing enteral feed compared with an isonitrogenous, isoenergetic control feed would influence outcome. The study endpoints were morbidity, mortality, and hospital cost at 6 mo postintervention. In one general intensive care unit (ICU), to ensure consistency of management policies, 78 critically ill adult patients with Acute Physiological and Chronic Health Evaluation (APACHE) II score of 11 and greater and who were considered able to tolerate introduction of enteral nutrition were studied. Fifty patients successfully received enteral nutrition (26 glutamine, 24 control). There was no mortality difference between those patients receiving glutamine-containing enteral feed and the controls. However, there was a significant reduction in the median postintervention ICU and hospital patient costs in the glutamine recipients $23,000 versus $30,900 in the control patients (P = 0.036). For patients given glutamine there was a reduced cost per survivor of 30%. We conclude that in critically ill ICU patients enteral feeds containing glutamine have significant hospital cost benefits.