Background: Dipeptide alanyl-glutamine is a commonly used substrate in major trauma patients. Its importance and effects are widely discussed; as yet, it has not been elucidated whether its administration influences glucose homeostasis. Objective: We studied the effect of alanyl-glutamine administration on insulin resistance. Design. Prospective, randomized, controlled trial. Setting: Intensive care unit of a tertiary level hospital. Patients: Multiple-trauma patients. Interventions, Patients were randomized into two groups and assigned to receive parenterally an equal dose of amino acids either with alanyl-glutamine in the dose of 0.4 g.kg body weight(-1).24 hrs(-1) (group AG) or without alanyl-glutamine (control group C). This regimen started 24 hrs after injury and continued for 7 days. To assess insulin sensitivity, we performed an euglycemic clamp on day 4 and day 8 after injury. Measurements and Main Results. We randomized 40 patients, 20 into each group. At day 4, insulin-mediated glucose disposal was higher in group AG (2.4 +/- 0.7 mg.kg(-1).min(-1) glucose), with significant difference from group C (1.9 +/- 0.6 mg.kg(-1).min(-1), p=.044). At day 8, glucose disposal was higher in group AG (2.2 +/- 0.7 mg.kg(-1).min(-1) glucose), with significant difference in comparison with group C (1.2 +/- 0.6, p <.001). Diminution of the main glucose homeostasis variables in group C between days 4 and 8 of the study was statistically significant (p <.001); however, differences in these variables in group AG were without statistical significance. Conclusions. Parenteral supplementation of alanyl-glutamine dipeptide was associated with better insulin sensitivity in multiple-trauma patients.