Objective: To study the impact of perioperative, enterally administered whey protein concentrate on infectious complications after major elective gastrointestinal surgery in a tertiary care hospital. Materials and Methods: Prospective non-randomized study conducted from June 2008 and ndash;April 2010, which included 50 consecutive patients who underwent major elective gastrointestinal surgery for benign and malignant diseases. The primary outcome measured was the rate of infectious complications, and the secondary outcome was length of postoperative stay. Results: 50 patients were divided into two equal groups: Group 1 and Group 2 (n=25 each). One group received immune-enhanced enteral nutrition (IMEN) perioperatively, and the control group received standard enteral nutrition (SEN) during the same period. There were no significant differences between the two groups with regard to complications (P=0.26), either infective (P=0.76) or non-infective (P=0.65). There was no significant difference in the duration of postoperative stay (P=0.25) between the two groups. There was also no significant difference in the pre- and postoperative White Blood Cell (WBC) count, C-Reactive Protein (CRP), and albumin levels. However, a subgroup analysis carried out to identify malnourished patients in the immunonutrition group revealed significant reduction in the length of postoperative stay (P=0.03) but not the rate of infectious complications (P=0.20). Conclusion: Perioperatively administered immunonutrition did not decrease the incidence of postoperative infectious complications and the duration of postoperative stay. Malnourished patients given immunonutrition in the perioperative period showed a significant reduction in the length of postoperative hospital stay but not the incidence of infective complications. [Arch Clin Exp Surg 2014; 3(1.000): 16-25]