Clostridioides difficile infection is reported to occur after 2.2% of colorectal operations and is associated with longer length of hospital stay, greater overall healthcare cost, and significant morbidity and mortality. The incidence of Clostridioides difficile infection is greatest after elective stoma reversal. The purpose of this study was to evaluate the effect of prior Clostridioides difficile infection on patients undergoing stoma reversal. We hypothesized that patients with a history of Clostridioides difficile infection who underwent stoma reversal will be at an increased risk of postoperative Clostridioides difficile infection compared with patients without a history of Clostridioides difficile infection.This was an observational cohort study of patients undergoing elective stoma reversal surgery by colorectal surgeons at a single academic institution during a 10-year period. A prospectively maintained institutional database was queried to identify 454 patients who underwent stoma reversal surgery between January 1, 2007 and December 31, 2017. The primary outcomes were Clostridioides difficile infection after stoma reversal and time to Clostridioides difficile infection after bowel refunctionalization. Secondary outcomes included postoperative complications, length of hospital stay, discharge destination, and 30-day readmission rate. Univariate and multivariable logistic regression analyses were conducted to identify factors associated with Clostridioides difficile infection after stoma reversal.A total of 445 patients were identified who underwent elective stoma reversal, 42 of whom had a history of Clostridioides difficile infection before the stoma reversal. There were no significant differences in patient age, number of days diverted, or use of perioperative antibiotics between patients with and without a history of Clostridioides difficile infection. The incidence of postreversal Clostridioides difficile infection was 23.4% in patients with a history of Clostridioides difficile infection compared with 9.6% in patients with no Clostridioides difficile infection history (P = .004); however, time to Clostridioides difficile infection after reversal did not differ. History of Clostridioides difficile infection was also associated with greater risk of postoperative complications (26.2% vs 9.4%, P.01), increased length of stay (3 vs 5 days postoperatively, P.01), increased likelihood of discharge to a skilled-care facility (11.9% vs 6.2%, P.01), and readmission (13.7 vs 31.0%, P.01) within 30 days. In a multivariable logistic regression model, history of Clostridioides difficile infection, increased length of hospital stay, and discharge to a skilled facility were associated with increased risk of Clostridioides difficile infection after reversal, while proton pump inhibitors use was associated with decreased risk of Clostridioides difficile infection.Patients with a prior history of Clostridioides difficile infection who underwent stoma reversal exhibited higher rates of postoperative Clostridioides difficile infection and were at greater risk of postoperative complications, discharge to a skilled facility, and 30-day readmission. Furthermore, research into interventions aimed at improving outcomes in this unique, high-risk population is needed.