OBJECTIVES: Clostridium difficile-associated disease (CDAD) is a nosocomial gastrointestinal infection that has been associated with increases in health care costs. Fidaxomixin was recently approved for CDAD but is costly compared to conventional agents. We evaluated the cost-effectiveness of fidaxomicin, metronidazole, and vancomycin in the treatment of CDAD. METHODS: A decision analysis model was created to estimate the cost-effectiveness of fidaxomicin, metronidazole, and vancomycin in clinical cure from the US health care payer perspective. Parameters for the model were determined from the published literature and indirect treatment comparison was performed using Bayesian methods to obtain the probabilities for responder and recurrence rates. Medication costs were determined from the AWP and resource costs were determined from CPT and HCPCS codes. All costs were adjusted for 2011 US dollars. Probabilities of responder and recurrence, costs, and resource utilization were fitted with a beta, gamma, and triangle distribution, respectively. Probabilistic sensitivity analysis with 10,000 trial simulations was performed to test the robustness of the model. Probabilities of cost-effectiveness for different treatment strategies were plotted on a cost-effectiveness acceptability frontier (CEAF). RESULTS: The total direct costs for fidaxomicin, metronidazole, and vancomycin were $14,219.98, $13,927.53, and $13,554.08, respectively. The cost-effectiveness ratio for the treatment of CDAD with fidaxomicin, metronidazole, and vancomycin were $16,903.12, $20,229.74, and $17,386.62 per clinical cure, respectively. Metronidazole was dominated by vancomycin. According to the CEAF, vancomycin has a cost-effectiveness probability of 0.4 at a WTP of $0/additional cure. At a WTP >$22,000/additional cure, however,fidaxomicin was more cost-effective. CONCLUSIONS: Fidaxomicin is cost-effective when the WTP is >$22,000/additional cure. At a WTP