Purpose: Recent guidelines for sepsis treatment emphasizes the need for early recognition of disease, leading to the development of the MEDS scoring system. However, there has been no prospective validation or comparison against other scoring systems. Therefore, we prospectively validated the MEDS scoring system and compared it with Multiple Organ Dysfunction Score (MODS) and Sepsis-related Organ Failure Assessment (SOFA) scoring systems. Methods: MEDS, MODS, and SOFA scores of 288 patients who were suspected to have systemic infection were calculated at the times of their emergency department visits, and clinical data of the patients were reviewed after six months. Results: MEDS, MODS, and SOFA scoring systems were all valid in the prediction of mortality according to logistic regression analysis. The results of probit analysis revealed significant and direct relationships between the scores and the mortality rate and demonstrated the parallelism of the mortality prediction of the three scoring systems. The cut-off values for the MEDS scoring system successfully divided subjects into five groups according to their risk for death. And the MEDS score well predicted the admission to ward or intensive care unit in survived patients. Conclusion: MEDS, MODS, and SOFA scor all were good predictors of outcome for patients with suspected sepsis and showed the same degree of predictive power. The MEDS scoring system, however, featured ease of calculation and definite clinical cut-off values which were useful in guiding decisions about treatment options. It also was well correlated with the prognosis of survived patients. We believe it to be the most useful and appropriate clinical prediction tool in cases of suspected sepsis in the emergency department.