Purpose: To study the influence of body position on the pulmonary surfactant system in multiple trauma patients with respiratory failure. Settings: University hospital, trauma intensive care unit (ICU). Design: Prospective, randomized. Patients and Methods: Multiple trauma patients (Injury Severity Score [ISS] > 17, Abbreviated Injury Scale Chest > 3) and primary admission were included, if the PaO2:FiO2 ratio decreased (< 300 mmHg, ≤ 24 h, or < 200 mmHg, ≤ 8 h) within 14 days after trauma. The patients were assigned to a supine (S: n = 9) or prone (P: n = 9) group. The study was terminated, if the PaO2:FiO2 ratio reached > 300 mmHg for > 24 h. Phospholipids, surfactant protein A, and surfactant function were determined in bronchoalveolar lavages at days 0, 1, 2, 5, and 14. Statistics: Mann-Whitney U-test, Fisher's exact test (p < 0.05). Results: The groups were comparable for age (P: 43 ± 3 years, S: 40 ± 5 years; p = 0.69) and ISS (P: 42 ± 11, S: 35 ± 9; p = 0.19). The prone group had more frequently a PaO2:FiO2 ratio < 200 mmHg at the time of inclusion (P: 8/9, S: 3/9; p = 0.05), a higher rate of liver failure (P: 5/9, S: 0/9; p = 0.02) and sepsis (P: 9/9, S: 3/9; p = 0.01), and a longer duration of ventilation (P: 51 ± 34 days, S: 26 ± 8 days; p = 0.03). The total amount of phospholipids and the single phospholipids were not different between the study groups. The surfactant function was altered in both groups without any statistical difference between the study groups. Conclusion: The prone position had no effect on surfactant composition, surfactant function, and the PaO2:FiO2 ratio within the observation period. © URBAN & VOGEL.