Ten severely injured patients who were admitted to the intensive care unit and who needed total parenteral nutrition (TPN) were randomly enrolled in a prospective double-blind study comparing two 20%-fat intravenous emulsions: one (MCT-LCT) containing a physical mixture of 75% medium-chain triglyceride (MCT) and 25% long-chain triglyceride (LCT) and another containing 100% LCT. TPN (30 kcal.kg-1.day-1) was given continuously as amino acids (20% of energy) and glucose (50% of energy) over 7 days with the respective lipid emulsion (30% of energy) provided from 0800 to 1600 each day. Plasma substrate concentrations, nitrogen balance, resting energy expenditure, substrate net oxidation rates, whole-body lipolysis rates, and fatty acid reesterification rates were measured or calculated. Plasma concentrations of lipid metabolites (glycerol, triglycerides, and fatty acids) indicated rapid hydrolysis and efficient use of the MCT-LCT emulsion. Whole-body lipolysis rate decreased by 53% in the MCT-LCT group and by 34% in the LCT group. Net fat oxidation was greater and FFA reesterification less with MCT-LCT than with LCT, indicating more efficient and rapid fuel utilization in the post-traumatic period with the MCT-LCT emulsion. In critically ill patients dependent on intravenous nutrition, an MCT-LCT mixture may be useful as an obligate fuel and to limit net hepatic lipogenesis.