OBJECTIVES: This study compared the costs and effectiveness of fidaxomicin and vancomycin for the treatment of Clostridium difficile infection (CDI). This analysis was conducted from a hospital perspective to assist health-care providers in deciding whether to add fidaxomicin to their formularies. METHODS: A decision tree model examined whether fidaxomicin or vancomycin is more cost-effective for treating CDI. Outcomes data for this analysis were obtained from OPT-80-003 Clinical Study Group (fidaxomicin versus vancomycin) clinical trial. The main outcomes were: clinical cure which is resolution of symptoms, recurrence of CDI, and global cure which is clinical cure with no recurrence. Cost data were per CDI patient: 10 days hospitalization costs ($17,196), 10 days fidaxomicin regimen costs ($2,800), and 10 days vancomycin regimen costs ($26.8). RESULTS: The baseline cost effectiveness analysis found that fidaxomicin was slightly more effective but more costly than vancomycin. That means that a hospital would pay an extra $31,539 if fidaxomicin were chosen to treat each episode of CDI. The model is most sensitive to hospitalization costs, which is coherent with the literature. A one-way sensitivity analysis on drug cost found that fidaxomicin did not dominate whatever the cost was. A two-way sensitivity analysis on hospitalization cost and the clinical cure rate of fidaxomicin found that vancomycin was only dominated when fidaxomicin cure rates reached 97%, and this is highly unlikely. CONCLUSIONS: Based upon this analysis, vancomycin is the recommended drug of choice for CDI treatment. The hospital would pay an extra $31,539 to treat each episode of CDI using fidaxomicin. Fidaxomicin would only be preferred if it had a higher clinical cure rate and a cheaper price according to the sensitivity analysis. As a conclusion, hospitals could consider fidaxomicin as second line treatment for cases in which patients have failed a course of treatment with vancomycin.