Background: Clostridium difficile infection (CDI) accounts for significant inhospital mortality. The purpose of this study was to validate a 9-point severity score index (SSI) at the time of diagnosis that could predict severity and mortality in CDI.Methods: Patients with positive toxin A/B were screened and enrolled within 48 hours of diagnosis. They were categorized based on SSI into mild, moderate, or severe disease. The Charlson Comorbidity Index (CCI) was calculated, and the patients were divided into the following categories: CCI 0, 1, Q 2 or greater. All patients were followed for a period of 90 days.Results: Fifty-four male patients were enrolled (mean age, 76.8 years).Mild, moderate, and severe disease was scored in 63%, 30%, and 7% of the patients, respectively. Low albumin (53.7%) and altered white blood cell count (46.3%) were the most common criteria. Need for intensive care unit care was more frequent with higher SSI (P G 0.05). Mortality rate correlated with disease severity (P = 0.005). The CCI score did not correlate with the severity of CDI; nevertheless, a CCI of 2 or greater had a direct association with overall mortality (P = 0.0001).Discussion: Severity score index measured at the time of diagnosis is a useful tool to assess severity and predict mortality. A high SSI score suggests the need for intensive care unit care in patients with CDI. Subsequent studies are needed to assess if SSI at the time of diagnosis should be used to determine the level of care and treatment strategies that may modify outcomes in this population.