Clostridium difficile infection (CDI) poses a substantial burden on patients with inflammatory bowel disease (IBD). This study aimed to explore the prevalence, associated factors, clinical course, and outcomes of CDI in patients with IBD at a tertiary hospital in Saudi Arabia. This retrospective case control study was conducted at Prince Mohammed bin Abdulaziz Hospital in Riyadh. All adult patients with IBD admitted over a 4 year period (2022-2025) were identified using the hospital’s electronic database. Participants who fulfilled the inclusion criteria were categorized into two groups: those with CDI and those without CDI. Logistic regression modeling was used to identify the predisposing factors for CDI. The study included 104 patients with IBD. Most patients (74%; 77/104) were diagnosed with Crohn’s disease (CD), whereas 26% (27/104) were diagnosed with ulcerative colitis (UC). The prevalence of CDI was 27.9% (29/104). Most of the CDI cases (65.5%, 19/29) were hospital-aquired. Further, CDI was more prevalent in older patients and female patients (P = 0.001 and P = 0.041, respectively). Patients with UC frequently had a higher risk of CDI than that of patients with CD. CDI-positive patients showed significantly higher previous exposure to antibiotics, steroid therapy, and immunosuppressants (P < 0.001). Binary analysis identified several significant predisposing factors for CDI, including UC, previous antibiotic use, corticosteroid use, and prolonged hospitalization (odds ratios = 15.338, 17.728, 35.255, and 16.614, respectively). Most patients (79.3%) recovered from CDI. Infection recurrence and death occurred in 10.3% cases each. CDI is a prevalent complication in hospitalized patients with IBD in Saudi Arabia. UC, prolonged hospitalization, antibiotic use, and corticosteroid therapy are important risk factors. Early recognition, targeted therapy, and preventive strategies must be considered to limit CDI and mortality.