Nosocomial infections are an important cause of morbidity and mortality in the surgical intensive care unit (SICU). Clinical benefits of glutamine‐supplemented parenteral nutrition may occur in hospitalized surgical patients, but efficacy data in different surgical subgroups are lacking. The objective was to determine whether glutamine‐supplemented parenteral nutrition differentially affects nosocomial infection rates in selected subgroups of SICU patients. This was a double‐blind, randomized, controlled study of alanyl‐glutamine dipeptide‐supplemented parenteral nutrition in SICU patients requiring parenteral nutrition and SICU care after surgery for pancreatic necrosis, cardiac, vascular, or colonic surgery. Subjects (n = 59) received isocaloric/isonitrogenous parenteral nutrition, providing 1.5 g/kg/d standard glutamine‐free amino acids (STD‐PN) or 1.0 g/kg/d standard amino acids + 0.5 g/kg/d glutamine dipeptide (GLN‐PN). Enteral feedings were advanced as tolerated. Nosocomial infections were determined until hospital discharge. Baseline clinical/metabolic data were similar between groups. Plasma glutamine concentrations were low in all groups and were increased by GLN‐PN. GLN‐PN did not alter infection rates after pancreatic necrosis surgery (17 STD‐PN and 15 GLN‐PN patients). In nonpancreatic surgery patients (12 STD‐PN and 15 GLN‐PN), GLN‐PN was associated with significantly decreased total nosocomial infections (STD‐PN 36 vs GLN‐PN 13, P < .030), bloodstream infections (7 vs 0, P < .01), pneumonias (16 vs 6, P < .05), and infections attributed to Staphylococcus aureus (P < .01), fungi, and enteric Gram‐negative bacteria (each P < .05). Glutamine dipeptide‐supplemented parenteral nutrition did not alter infection rates following pancreatic necrosis surgery but significantly decreased infections in SICU patients after cardiac, vascular, and colonic surgery.