Introduction: Two large, placebo-controlled phase III trials, MODIFY I and MODIFY II, demonstrated that patients with Clostridioides difficile infection (CDI) treated with bezlotoxumab (BEZ) had a lower rate of recurrent infection than placebo. The clinical efficacy of BEZ has been evaluated in real-world studies. We aimed to carry out a systematic review and meta-analysis of the efficacy of BEZ in real-world clinical setting. Methods: A thorough search of literature was run on February 2022, in Cochrane Central Register of Controlled Trials, Embase, Medline, Scopus and Web of Science Core Collection. We included studies that reported CDI resolution rates with BEZ. The random-effects model described by DerSimonian and Laird was used to calculate weighted pooled resolution rates (WPR) with corresponding 95% confidence intervals (CI). Data were weighted based on the sample size in each trial to calculate WPR. We assessed heterogeneity within groups with the inconsistency index (I2) statistic. The primary outcome of our pooled analysis was CDI clinical resolution rates with BEZ i.e. resolution of CDI with no recurrence in the follow up period. Results: Thirteen studies (11 retrospective cohorts, 2 unspecified) including 1008 CDI patients were included. Recurrence with BEZ was compared with standard-of-care (SOC) antibiotics (metronidazole, vancomycin or fidaxomicin) in 6 studies and with fecal microbiota transplantation (FMT) in 1 study, the other 6 had no comparator arm. A total of 771 patients received BEZ, 237 received SOC and 14 received FMT. Patients were followed for recurrence for a median of 90 days from initial episode (range 84-168 days). Of the 771 on BEZ, 550 had CDI resolution with WPR of 82% (95% CI 79-85%). No significant heterogeneity was noted, with I2=0% (Figure). A resolution rate of 50% (7/14) was seen in the FMT group. Subgroup analysis comparing BEZ with SOC revealed a WPR of 84% (95% CI 79-89%) with BEZ vs 67% (95% CI 61-73%) with SOC (p=0.0001). Conclusion: Use of BEZ in real-world clinical settings seems to have a high resolution rate of CDI in patients with recurrence.Figure 1.: Forest plot depicting weighted resolution rate observed with bezlotoxumab