Background: The incidence of Clostridioides difficile infection (CDI) has increased in recent years in patients with inflammatory bowel disease (IBD). C. difficile is a toxin-producing bacterium, and CDI results in the worsening of underlying IBD, increasing the risk of IBD treatment failure, surgery, and hospitalization. Because the symptoms of CDI overlap with those of IBD, it is challenging to make a differential diagnosis. Therefore, early, rapid, and reliable diagnostic tools that can identify CDI in IBD patients would be valuable to clinicians. Methods: This study retrospectively collected 135 patients with IBD. Among them, 44 patients were diagnosed with CDI, and 42 patients were diagnosed with viral or fungal infections. A total of 49 patients without infections were defined as the control group. The diagnostic values of procalcitonin (PCT), C-reactive protein (CRP), and white blood cell (WBC) count in the peripheral blood were examined. Results: In this study, PCT levels were significantly higher in patients with CDI than in non-CDI patients (including patients with viral/fungal infections and the control group; p < 0.001 and p < 0.05, respectively). CRP levels were significantly higher in patients with CDI than in non-CDI patients (p < 0.05). The area under the curve (AUC) of PCT and WBC count were compared using DeLong's test: the AUCs of PCT vs. CRP for the detection of the IBD-CDI group and the control group was 0.826 [95% confidence interval (CI) 0.743-0.909] vs. 0.663 [95% confidence interval (CI) 0.551-0.774] (p < 0.05), respectively. WBC count was inferior as a diagnostic tool for CDI. The sensitivity was 59.09% (95% CI: 43.2% to 73.7%), the specificity was 89.80% (95% CI: 77.8% to 96.6%), and the positive likelihood ratio LR (+) was 5.79 for PCT for the diagnosis of CDI. Conclusions: The present study demonstrates the superiority of PCT over CRP and WBC count for the rapid diagnosis of CDI in IBD patients.