Endogenous arginine vasopressin (AVP) levels in multiple trauma patients are unknown. Arginine vasopressin is considered to play an important role in severe hemorrhage. In this prospective study, 87 multiple trauma patients (Injury Severity Score >15) and 50 healthy volunteers were enrolled. On admission to the emergency department (ED), demographic, clinical, and laboratory data were documented, and blood was sampled for determination of AVP (radioimmunosassay) and copeptin, a stable fragment of the AVP precursor (immunoluminometric assay). In patients requiring intensive care unit (ICU) therapy, blood and data sampling were repeated at 4, 6, and 24 h after ED admission. Linear logistic and mixed-effects regression analyses were used for statistical analysis. On ED admission, AVP plasma concentrations (43.2 +/- 84.9 pM) were significantly increased when compared with controls (0.92 +/- 0.44 pM, P < 0.001). Plethysmographic oxygen saturation was the only parameter independently associated with AVP (regression coefficient, -0.126; 95% confidence interval, -0.237 to -0.014; P = 0.03). No correlation was observed between AVP and survival (P = 0.62), hemodynamic variables (systolic arterial pressure, P = 0.24; MAP, P = 0.59; diastolic arterial pressure, P = 0.74; central venous pressure, P = 0.36), or brain trauma (P = 0.46). In ICU patients, AVP decreased during the first 24 h (P < 0.001) and was independently associated with heart rate (P = 0.02) and blood glucose (P = 0.009). Copeptin concentrations were correlated with AVP (r2 = 0.718, P < 0.001). In conclusion, AVP was significantly increased in multiple trauma patients and seems to be an integral part of the neuroendocrine response to severe injury. In ICU patients, AVP decreased to moderately elevated levels within 24 h after ED admission.