We prospectively evaluated serum procalcitonin concentrations in patients who presented to an emergency department (ED) with suspected infectious or inflammatory disease. Of 195 study patients, 68 had final diagnosis of systemic infection, and 24 of those 68 had elevated serum procalcitonin levels (>0.5 ng/mL). The procalcitonin level had a sensitivity of 0.35 and specificity of 0.99 for the diagnosis of systemic infection. In multivariate analysis, the procalcitonin level was the only independent variable associated with this diagnosis; in contrast, the C-reactive protein level was not. All patients with systemic infections who ultimately died had procalcitonin levels of >0.5 ng/mL at admission. Procalcitonin levels were significantly higher in patients who ultimately died of systemic infection than in patients who survived. The optimal procalcitonin threshold for the ED population may be lower than that proposed for critically ill patients. Determination of the procalcitonin level may be useful for screening and prognosis of more-severely ill ED patients.