Reducing rehospitalization has been a primary focus of hospitals and payors. Recurrence of Clostridioides difficile infection (CDI) is common and often results in rehospitalization. Factors that influence rehospitalization for CDI are not well understood. To determine the risk factors that influence rehospitalization caused by CDI. A retrospective cohort study from January 1, 2018, to December 31, 2018, of patients aged ≥18 who tested positive for C. difficile while hospitalized. Academic hospital. The risk of rehospitalization was assessed across exposures during and after the index hospitalization using a Cox proportional hazards model. The primary outcome of this study was 60-day CDI-related rehospitalization. There were 559 hospitalized patients with a positive CD test during the study period, and 408 patients were included for analysis. All-cause rehospitalization was 46.1% within 60 days of the index hospital discharge. Within 60 days of discharge, 68 patients developed CDI, of which 72.5% (49 of 68) were rehospitalized specifically for the management of CDI. The risk of rehospitalization in patients with CDI was higher among patients who were exposed to systemic antibiotics ([adjusted hazard ratio] aHR: 2.78; 95% CI, 1.36-5.64) and lower among patients who had post-discharge follow-up addressing C. difficile (aHR: 0.53; 95% CI, 0.28-0.98). Exposure to systemic antibiotics increased the risk of rehospitalization due to CDI, while post-discharge follow-up decreased the risk of rehospitalization due to CDI. Comprehensive transitions of care for hospitalized patients with C. difficile may reduce the risk of CDI-related rehospitalization.