current studies suggest immunonutrition decreases the inflammatory process, infection rates and reduces length of hospital stay in surgical patients, however studies are often conducted on heterogeneous groups of patients with varying composition of the immuno-nutrition. We aim to investigate the effect of immunonutrition on patients undergoing major upper gastrointestinal surgery by assessment of (i) the inflammatory and immune response and (ii) changes in clinical outcome when compared to a randomised control receiving conventional feeding. a prospective double-blind randomised controlled study was undertaken to compare a feed supplemented with glutamine, arginine, -3 fatty acids and tributyrin, vitamin C, E and B-carotene and micronutrients (zinc, selenium and chromium) to an isonitrogenous, isocaloric control feed in patients undergoing major upper GI surgery. The primary end-points were defined as C-reactive protein (CRP), prealbumin and retinol binding protein (RBP) levels. Secondary end-points included performance scoring systems, length of hospital stay, adverse events and protein and nutrient assays. Variables were measured pre-operatively and routinely up to the 4th post-operative day. there was no statistically significant change in primary end-points between the immunonutrition group and the control group. There was no difference in length of hospital stay between the groups. The vitamin C level in the study group was significantly higher at the end of the study period. Both groups tolerated the feeds well with adequate target feeding rate. There were no other significant changes in clinical outcomes between the two groups. this study has not shown a benefit of immunonutrition through changes in inflammatory or nutritional markers, a decrease in length of hospital stay, or other morbidity. This may be because of inadequate numbers recruited to the study. Further, multi-centre, randomised trials on homogeneous patient groups are necessary to investigate the role of immunonutrition in major upper GI surgery.