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Clostridium difficile infection (CDI) is treated most often with metronidazole or vancomycin. Both have been effective in treatment of mild to moderate infection. In more severe cases, vancomycin may be more effective.The primary objectives were to quantify the severity of CDI and to describe overall adherence to the institutional CDI guideline. Secondary objectives were to assess factors associated with adherence to the guidelines.Retrospective analysis of the electronic medical record was used to evaluate adherence to institutional guidelines. Data collected included demographics and other factors potentially contributing to adherence: Charlson comorbidity index, severity of infection, recurrence, intensive care unit (ICU) admission, infectious diseases (ID) consult, total duration and number of antibiotics, alternative therapies, and acid suppression. Descriptive statistics and bivariate analyses were used to describe and compare factors associated with guideline adherence; multivariate logistic regression assessed independent predictors of adherence.A total of 387 patients met the inclusion criteria. CDI severity was 55.8% mild/moderate cases, 42.4% severe, 0.5% fulminant, and 1.3% prophylaxis. Overall, institutional guideline adherence was 51.9%. In bivariate analyses, 5 factors were associated with nonadherence to guidelines: older age, ICU admission, duration of antibiotics, mild/moderate and severe infection (all P < .05). In the logistic regression model, severe infection (P < .001) and longer duration of antibiotics (P < .05) were independently associated with guideline nonadherence.In this study, 42.4% of the patients met criteria for severe infection. Providers for patients with severe infection and longer duration of antibiotic therapy were less likely to adhere to the institutional guideline.