OBJECTIVES: The purpose of this cost-effectiveness model is to compare the cost-effectiveness of metronidazole, oral vancomycin, fidaxomicin, and fecal transplants for CDI. METHODS: This is a cost-effectiveness model from the societal perspective using probabilities, cost, and utility parameters from scientific literature. A decision tree model for mild/moderate CDI compares metronidazole, oral vancomycin, fidaxomicin, and fecal transplant. A decision tree for severe CDI compares oral vancomycin, fidaxomicin, and fecal transplant. Both decision trees capture up to two recurrences and/or the necessity of a colectomy. Both models account for short-term and long-term costs of CDI. One-way sensitivity and threshold sensitivity analysis were used to assess the robustness of the data. RESULTS: For mild-moderate CDI, fecal transplant is a dominant treatment option, as it reduces costs to $13,537 and increases effect to 11.85 QALYs. The best alternative to fecal transplants in mild-moderate disease is fidaxomicin if WTP/QALY >$0. For severe disease, fecal transplant is still a dominant treatment option, as it reduces costs to $13,537 and increases effect to 11.84 QALYs. The best alternative to fecal transplants in severe CDI is oral vancomycin at all WTP/QALY. For mild-moderate disease indicated that fecal transplants are favored to fidaxomicin as long as the cost of fecal transplants < $4,515, fecal transplant cure rate > 0.883, fecal transplant recurrence rate < 0.185, fidaxomicin cure rate < 0.955, and fidaxomicin recurrence rate > 0.02. For severe disease indicated that fecal transplants are favored to oral vancomycin as long as the cost of fecal transplants < $4,860, fecal transplant cure rate > 0.79, and the fecal transplant recurrence rate < 0.36. CONCLUSIONS: In both the treatment of mild/moderate and severe CDI, it is cost-effective to use fecal transplants as standard protocol rather than the last resort.