Background: Patients with upper gastrointestinal (GI) tract malignancies are at risk for malnutrition and postoperative morbidity and mortality. We examined the protein kinetic effects of early enteral feeding in this population and compared it with results in patients receiving IV fluid. Methods: Twenty-nine patients undergoing resection of an upper GI tract malignancy were prospectively randomized to either enteral feeding starting on postoperative day (POD) 1 via a jejunostomy tube (FEED, n = 12) or IV fluid (IVF, n = 17). On POD5, all patients underwent a protein metabolic study using [3Hlphenylalanine to determine forearm skeletal muscle (nmol phenylalanine/100 g/min) protein net balance. Free fatty acids (FFA, mEq/dL) and insulin levels (mU/mL) were measured. Results: Protein net balance was significantly less negative in the FEED group compared with the IVF group (- 1.4 ± 0.8 vs -5.0 ± 1.4, p < .05). Respiratory quotient was significantly increased in patients receiving enteral feeding (0.85 ± 0.02 vs 0.78 ± 0.02 FEED vs IVF, p < .05). FFA levels were significantly decreased in the FEED group (0.36 ± 0.04 vs 0.85± 0.07, p < .05). Insulin levels were significantly elevated in the FEED group (19.8 ± 4.5 vs 9.3 ± 0.8, p < .05). Insulin levels correlated with amino acid fluxes. Conclusions: Postoperative enteral nutrition in upper GI cancer patients results in an improvement in protein kinetic net balance and amino acid flux across peripheral tissue. In addition, insulin levels are elevated, and this elevation correlates with amino fluxes across the forearm. By improving peripheral protein kinetics, early postoperative enteral nutrition may potentially contribute to a decrease in postoperative morbidity and mortality in upper gastrointestinal cancer patients.