OBJECTIVES: Clostridium difficile is the most common cause of hospital-acquired diarrhea in Australia. In 2013, a randomized controlled trial demonstrated the effectiveness of fecal microbiota transplantation for the treatment of recurrent Clostridium difficile infection. The aim of this study is to evaluate the cost-effectiveness of fecal microbiota transplantation compared with vancomycin for the treatment of Clostridium difficile infection in Australia. METHODS: A Markov model was developed to compare the cost-effectiveness of fecal microbiota transplantation compared with standard antibiotic therapy. A literature review of clinical evidence informed the structure of the model and the choice of parameter values. Clinical effectiveness was measured in terms of quality adjusted life years. Uncertainty in the model was explored using probabilistic sensitivity analysis. RESULTS: Using fecal microbiota transplantation rather than vancomycin saves AU$7,425 (95% CI: AU$2,252, AU$12,598) per Clostridium difficile infection patient. Fecal microbiota transplantation also leads to an incremental increase of 1.02 (95% CI 0.23, 1.81) life-years or 0.87 (95% CI 0.06, 1.68) quality adjusted life years per patient compared with vancomycin. CONCLUSIONS: Based on current evidence, fecal microbiota transplantation is cost saving compared with standard antibiotic therapy for the treatment of recurrent Clostridium difficile infection. More research into the long-term safety and quality of life outcomes for patients receiving fecal microbiota transplantation is warranted.