BACKGROUND: Patients with upper gastrointestinal (GI) tract malignancies are at increased risk for malnutrition, as well as postoperative morbidity and mortality. As data clearly documenting the benefit of early postoperative enteral feeding in upper GI cancer patients as compared with no feeding are sparse, we examined the protein kinetic effects of early enteral feeding and compared it with standard postoperative care (ie, intravenous fluid). METHODS: Twenty-nine patients undergoing resection of an upper GI tract malignancy were prospectively randomized to either enteral feeding (FEED, n = 12) starting on postoperative day (POD) 1 via a jejunostomy tube or intravenous fluid (IVF, n = 17). On POD 5, all patients underwent resting energy expenditure determination and a protein metabolic study using the isotope 14C-leucine to determine whole body (WB, μmol leu/kg/min) protein kinetics. RESULTS: Respiratory quotient and insulin (μU/mL) levels were significantly increased in patients receiving enteral feeding (0.85 ± 0.02, 19.8 ± 4.5 versus 0.78 ± 0.02, 9.3 ± 0.8, FEED versus IVF, P < 0.05). Free fatty acids (meq/dL) were significantly lower in FEED group (0.36 ± 0.04) as compared with IVF group (0.85 ± 0.07, P < 0.0001). While there were no significant differences in WB protein oxidation (0.10 ± 0.01 versus 0.10 ± 0.02) or synthesis (0.81 ± 0.09 versus 0.68 ± 0.08, IVF versus FEED), WB protein catabolism was significantly less (0.91 ± 0.10 versus 0.37 ± 0.09, P = 0.002), and WB protein net balance was converted to positive in FEED group (-0.10 ± 0.01 versus 0.30 ± 0.03, IVF versus FEED, P < 0.001). CONCLUSIONS: Early enteral feeding decreases fat oxidation and whole body protein catabolism while improving net nitrogen balance. By significantly improving protein metabolism, enteral feeding may decrease postoperative morbidity and mortality in upper GI cancer patients.