OBJECTIVE:To determine the effect of a low-calorie parenteral nutrition (PN) regimen on the incidence and severity of hyperglycemia and insulin requirements. DESIGN:Prospective, randomized, clinical trial. SETTING:Urban, university-affiliated, level-I trauma center. PATIENTS:Consecutive surgical patients requiring PN. INTERVENTIONS:Patients were randomized to receive either a low-calorie PN formulation (20 nonprotein kilocalories per kg per day) or a standard PN formulation (30 nonprotein kilocalories per kg per day). Lipid-derived calories were standardized to 1000 kilocalories three times weekly for all patients; consequently, the number of calories varied only by the amount of carbohydrate administered. Protein requirements were individualized on the basis of estimated metabolic stress. Hyperglycemia was defined as a blood glucose level ≥200 mg/dL. MEASUREMENTS AND MAIN RESULTS:Forty patients were evaluated (low-calorie PN, n = 20; standard PN, n = 20). Demographics of the two groups were similar. The incidence of hyperglycemic events was significantly lower in the low-calorie group (0% 0–0.5 vs. 33.1% 0–58.4; p = .001. Additionally, the severity of hyperglycemia was also lower in the low-calorie group (mean glucose area under the curve = 118 ± 22 mg·hr/dL vs. 172 ± 44 mg·hr/dL; p < .001). This resulted in lower average daily insulin requirements (0 0–0 units vs. 10.9 0–25.6 units; p < .001.). The only predictor of hyperglycemia was a dextrose administration rate >4 mg/kg/min. CONCLUSIONS:Administration of a low-calorie PN formulation resulted in fewer and less-severe hyperglycemic events and lower insulin requirements. PN regimens should not exceed a dextrose administration rate of 4 mg/kg/min to avoid hyperglycemic events.