Ventilator-associated pneumonia is a clear risk factor for acute lung injury which has been poorly described in trauma patients. This prospective study was undertaken to estimate the incidence of such ventilator-associated pneumonia leading to acute lung injury, the risk factors, and the associated morbidity and mortality in a group of multiple trauma patients. Trauma patients who were mechanically ventilated and survived at least 24 h were included. Ventilator-associated pneumonia was confirmed by a bacterial culture of a blind protected telescoping catheter with at least 10 colony-forming units/ml of at least one pathogen. Episodes of acute lung injury were prospectively recorded. Ventilator-associated pneumonia was documented in 78 patients of the 175 included (44%) and led to the development of ventilator-associated pneumonia acute lung injury in 18 patients (23%). The sole independent risk factor for ventilator-associated pneumonia leading to acute lung injury was the presence of Haemophilus influenzae (hazard ratio, 8.8; 95% confidence interval, 2.7-28.6). Eleven (61%) of the 18 patients with ventilator-associated pneumonia leading to acute lung injury had development of a ventilator-associated pneumonia recurrence, as compared with 20 (33%) of the 60 patients with ventilator-associated pneumonia alone (P = 0.03). Seven (39%) of the 18 trauma patients with ventilator-associated pneumonia leading to acute lung injury died, as compared with 9 (15%) of the 60 trauma patients with ventilator-associated pneumonia alone (P = 0.04). Acute lung injury complicated the course of 15% of ventilator-associated pneumonia in trauma patients. H. influenzae seemed to be one of the most frequent bacteria involved and the sole risk factor identified. Occurrence of ventilator-associated pneumonia leading to acute lung injury modified the prognosis of trauma patients.