Fecal microbiota transplantation (FMT) represents a cost-effective strategy for first recurrence of Clostridioides difficile infection (CDI), according to findings published in Clinical Infectious Diseases. Elizabeth S. Aby, MD, and colleagues created a model to simulate patients with initial CDI, estimating costs, effectiveness, and cost-effectiveness of CDI treatment regimens recommended in the 2021 IDSA guidelines, with the additional option of FMT for first recurrent CDI. When FMT was an option for first recurrence of CDI, the best cost-effective treatment strategy was fidaxomicin for a first, non-severe case of CDI; vancomycin for initial CDI that is severe; and FMT for first and subsequent recurrences of CDI, with an incremental cost-effectiveness ratio of $27,135 per quality-adjusted life year. Based on a probabilistic sensitivity analysis at a $100,000 cost-effectiveness threshold, FMT for first and subsequent CDI recurrences was cost-effective 90% of the time given parameter uncertainty. Prospective analysis of FMT for a first CDI recurrence is warranted, Dr. Aby and colleagues noted.