OBJECTIVE In mechanically ventilated patients, pulmonary gas exchange was investigated during the administration of total parenteral nutrition containing medium-chain triglycerides or long-chain triglycerides as fat emulsions. METHODS Prospective, randomized, crossover trial (two lipid infusion periods of 8 hrs). METHODS Intensive care unit in a university hospital. METHODS Six mechanically ventilated patients, using the pressure-support mode. METHODS Total caloric intake was adapted according to measured energy expenditure. Fat emulsion provided 50% of the energy expenditure. Patients were infused with 50% medium-chain/50% long-chain triglycerides or 100% long-chain triglycerides in a random sequence. RESULTS Oxygen consumption, CO2 production, and minute ventilation were measured by indirect calorimetry. PaO2 and PaCO2 were determined in blood samples. Medium-chain triglycerides increased oxygen consumption by 27.8% and minute ventilation by 14.3% at the end of the protocol. CO2 production, PaO2, and PaCO2 were not different between groups. CONCLUSIONS Medium-chain triglycerides cause an increase in metabolic demand in mechanically ventilated patients when they are infused over a short period. Postoperative or intensive care unit patients with a low pulmonary reserve should receive infusions of medium-chain triglycerides over a more prolonged period than long-chain triglycerides.