The 2021 focused update to the Infections Diseases Society of America/Society for Healthcare Epidemiology of America (IDSA/SHEA) guidelines for management of Clostridioides difficile infection (CDI) prioritizes the use of fidaxomicin over vancomycin for the treatment of initial and recurrent CDI. These recommendations have significant clinical and financial ramifications for hospitals and patients with CDI. Antimicrobial stewardship programs must balance the needs, goals, and barriers faced by patients and health systems when determining the best treatment strategy for CDI. In this commentary, we provide antimicrobial stewardship programs with a decision-making framework that acknowledges the fundamental principles of ethics to provide equitable patient care.