BACKGROUND The purpose of this study was to identify the burden and risk factors for inappropriate Clostridioides difficile infection (CDI) testing. METHODS This was a retrospective cohort study among adults hospitalized between 2010 and 2019. Inappropriate CDI testing was defined as a formed stool specimen, an order within 7 days of a previously negative test, or an order within 24 hours of laxative administration. RESULTS A total of 51,302 CDI orders were placed for 29,840 unique patients. 59% were appropriate and 41% were inappropriate. An additional 24% of the appropriate orders never resulted. Risk factors for inappropriate testing included orders placed by a nurse practitioner, orders placed by high-ordering providers, specific hospital units, fever, and leukocytosis. CONCLUSIONS Nearly half of all CDI orders were inappropriate among hospitalized patients, and an additional 24% of test results never returned. Provider- and patient-level risk factors included type of provider, specific hospital units, and signs of sepsis.