Background: Clostridioides difficile (C. difficle) infection (CDI) in inflammatory bowel disease (IBD) patients can be recurrent, resulting in poor outcomes, but the molecular characterization of C. difficle in IBD patients remains to be well-established in China. This study aimed to investigate the molecular epidemiology of C. difficile in adult and pediatric IBD patients in China. Methods: C. difficile strains were isolated and identified from the fecal samples of adult and pediatric IBD patients. Toxigenic strains were typed using multilocus sequence typing (MLST), and susceptibility to 10 antimicrobials was evaluated using E-test.Results: Among the 838 IBD patients, 96 (11.5%) patients were positive for CDI, which comprised of 53 adult (9.6%) and 43 children (14.9%) cases. Isolates positive for both toxin A and toxin B genes (A+B+) accounted for 90.2% (74/82), while the remaining 9.8% were negative for toxin A, but positive for toxin B (A–B+). These toxigenic strains were susceptible to metronidazole and vancomycin, but highly resistant to clindamycin, levofloxacin, erythromycin and ciprofloxacin. Furthermore, the isolates obtained from pediatric patients had a significantly higher resistance rate to clindamycin, when compared to isolates obtained from adult CDI (p=0.009). In addition, these toxigenic strains were categorized as 18 sequence types (STs). The dominant types consisted of ST-35 (20.7%), ST-2 (17.1%), ST-54 (13.4%) and ST-3 (13.4%) in all patients, ST-2 (19.6%), ST-35 (15.2%) and ST-54 (13.0%) in adult patients, and ST-35 (27.8%), ST-3 (19.4%), ST-2 (13.9%), ST-54 (13.9%) and ST-37(8.3%) in pediatric patients, respectively. All isolates formed three distinct clusters in the phylogenetic analysis. Conclusions: The incidence and molecular epidemiology of C. difficile infection in adult IBD patients resembled CDI in the general inpatient population. A higher antibiotic resistance rate was identified among the C. difficile isolates obtained from pediatric IBD patients, and few STs accounted for most multidrug-resistant strains. However, the molecular genetic features of the same ST-type between these two groups remained highly correlated.