OBJECTIVES In recent years a number of infections caused by Clostridium difficile has been significantly increasing. In Poland oral metronidazole constitutes the therapy of choice of non-severe infection and first-recurrence, while oral vancomycin is recommended to be given in case of severe disease and subsequent recurrences.  Fidaxomicin is a novel treatment for Clostridium difficile infections (CDI). The aim of this study was to perform a cost-utility analysis of fidaxomicin for the treatment of severe CDI compared  to vancomycin.  METHODS A meta-analysis of two randomized clinical trials phase III comparing oral fidaxomicin and oral vancomycin in CDI was conducted. A Markov model was used to determine the cost-utility of fidaxomicin in patients with severe CDI. The cycle length was 10 days and the time horizon was 1 year. The patient entered the model in the severe CDI health state and was given either fidaxomycin or vancomycin for 10 days. The analysis was performed from the third-party payer perspective – the Polish National Health Fund. Only direct healthcare costs (drug costs, hospitalization) were included. Given the lack of formal utility measures for CDI, the utilities for the alternative health states described in the literature were adapted.  RESULTS In the base case, fidaxomicin was dominant compared to vancomycin, resulting in cost savings of PLN 905 and an incremental QALY gain of 0.015. Fidaxomicin was associated with higher cost savings (PLN 30,883) assuming that patients with severe CDI would be hospitalized at intensive care unit. One-way sensitivity analyses revealed that fidaxomicin remained dominant even if considering marginal values of both antibiotics’ acquisition  cost.  CONCLUSIONS Fidaxomicin was dominant compared to vancomycin, generating additional QALYs with cost-savings in severe CDI patients in Poland.