To assess energy balance in very sick medical patients requiring prolonged acute mechanical ventilation and its possible impact on outcome, we conducted an observational study of the first 14 d of intensive care unit (ICU) stay in thirty-eight consecutive adult patients intubated at least 7 d. Exclusive enteral nutrition (EN) was started within 24 h of ICU admission and progressively increased, in absence of gastrointestinal intolerance, to the recommended energy of 125·5 kJ/kg per d. Calculated energy balance was defined as energy delivered 2 resting energy expenditure estimated by a predictive method based on static and dynamic biometric parameters. Mean energy balance was 25439 (SEM 222) kJ per d. EN was interrupted 23 % of the time and situations limiting feeding administration reached 64 % of survey time. ICU mortality was 72 %. Non-survivors had higher mean energy deficit than ICU survivors (P¼ 0·004). Multivariate analysis identified mean energy deficit as independently associated with ICU death (P¼0·02). Higher ICU mortality was observed with higher energy deficit (P¼ 0·003 comparing quartiles). Using receiver operating characteristic curve analysis, the best deficit threshold for predicting ICU mortality was 5021 kJ per d. Kaplan -Meier analysis showed that patients with mean energy deficit^5021 kJ per d had a higher ICU mortality rate than patients with lower mean energy deficit after the 14th ICU day (P¼ 0·01). The study suggests that large negative energy balance seems to be an independent determinant of ICU mortality in a very sick medical population requiring prolonged acute mechanical ventilation, especially when energy deficit exceeds 5021 kJ per d. Energy balance: Enteral nutrition: Acute prolonged mechanical ventilation: OutcomeNutritional support is based on the assumption that critically ill patients are prone to develop malnutrition, especially protein-energy deficit, this condition being associated with morbidity and mortality (1 -5) . Indeed, protein-energy deficit seems common in intensive care units (ICU), occurring in 43 -88 % of critically ill patients (6,7) . Underfeeding has been reported as associated with an increased rate of infection, poor wound healing, reduced respiratory muscle mass, delayed weaning from mechanical ventilation, increased length of ICU stay and increased health care costs (1,8 -13) . Perturbations of the normal metabolic response to starvation with hyperglycaemia, high lactate level, hypertriglyceridaemia and high NEFA concentrations due to insulin resistance characterize the hypermetabolic state of the critically injured patients (2,14,15) . Energy deficit results from a combination of hypermetabolism and reduced intake due to frequent interruptions in feedings because of gastrointestinal intolerance, diagnostic and therapeutic procedures (16 -18) . In intubated and mechanically ventilated patients, the great variability of resting energy expenditure (REE) and nutrient delivery compared to prescription, partly due to frequent use of sedatives, analgesic...