We examined whether procalcitonin (PCT) or neopterin (NT) are useful in predicting sepsis, multiple organ failure (MOF), or death after multiple trauma (MT). In a prospective clinical study, a total of 137 consecutive trauma patients (mean age 39 years, median injury severity score [ISS] 27 points) and 34 healthy volunteers were enrolled. Blood samples were collected on arrival in the emergency room until day 28 after trauma. Plasma NT was detected by enzyme-linked immunoassay and PCT plasma levels were determined using an immunoluminometric assay. The incidence of sepsis was 65%, MOF 48%, and death in hospital within 28 days 11%. After adjustment for age, gender, and ISS, PCT and NT levels during the first 2 days after injury were unable to differentiate between patients who developed sepsis or not. On the contrary, patients who developed MOF had higher PCT plasma levels on day 0 (0.60 vs. 0.15 ng/mL), and on days 1 and 2 combined (1.95 vs. 0.32 ng/mL). This difference remained significant in multivariate logistic regression (P = 0.01) and additional subgroup analyses for early and late MOF (P = 0.048 and 0.002). For NT, smaller differences were observed (4.39 vs. 3.68 nmol/L, and 7.20 vs. 5.79 nmol/L), which lost significance in multivariate analysis. On the basis of PCT, ISS, and age, a MOF prediction rule was developed and had a good predictive power (area under the curve: 0.77; P < 0.001). These findings demonstrate that high plasma concentrations of PCT in the early posttraumatic phase are an independent predictor of MOF but not of sepsis.