To analyze the clinical data of patients with recurrent Clostridioides difficile infection (rCDI) in the southwestern region, and help clinicians identify high-risk populations early and adopt appropriate treatment strategies. Methods Clinical data of rCDI cases from a tertiary first-class hospital in southwest China from July 2019 to June 2024 were collected, and their host-related risk factors, exogenous risk factors, treatment schemes, and endpoint outcomes were analyzed. Results In the past five years, a total of 26 cases of rCDI were detected from a ter-tiary first-class hospital in southwest China, accounting for 4.04% of the total positive cases (n=643) detected during the same period. 19.23% of the recurrent patients experienced a second recurrence. The median age of rCDI patients was 66.5 years old, with males accounting for 73.08%.The major comorbidity included diabetes mellitus (34.62%), malignant tumors (30.77%), and chronic renal diseases (23.08%). In the 8 weeks before the first onset of rCDI in patients, the top three drugs used were β-lactam and enzyme inhibitor compound (69.23%), proton pump inhibitors (65.38%), and carbapenems (46.15%). In the initial treatment of recurrent patients, 3.85% (1/26) of the cases were treated with metronidazole, 19.23% (5/26) of the cases received non-standard vancomycin/norvancomycin treatment in usage or dosage, 46.15% (12/26) of the cases received treatment with course less than 10 days. In the treatment of the first recurrence, 34.78% (8/26) of the cases received treatment with course less than 10 days. Conclusion For elderly patients and patients with diabetes mellitus, malignant tumors, and chronic renal diseases, who have used β-lactam and enzyme inhibitor compound, proton pump inhibitors, carbapenems within 8 weeks before disease onset, standard dose and treatment course of vancomycin or norvancomycin are recommended under permitted conditions, so as to reduce the risk of recurrence.