Background: Clostridioides difficile (C. difficile) is an anaerobic bacterium associated with considerable wide-spectrum colonic infections. Various risk factors are recognized to increase the incidence of C. difficile infection (CDI) in certain age groups. COVID-19 pandemic and its association with CDI remains an area of research. Objectives: Our aim is to investigate the risk factors and outcomes of CDI among hospitalized patients with diarrhea with special consideration for COVID-19 patients. Results: The study included 1515 hospitalized patients with infectious diarrhea from 2017 to 2021, 195 (13%) of them had positive CDI tests and 1320 (87%) were CDI-negative. The risk for CDI was higher in the young adults aged between 18 and 35years (OR: 2.47, 95%CI: 1.37- 4.47, p=0.0028) and older patients aged ≥ 56 years (OR: 1.95, 95% CI: 1.87-3.21, P=0.0084). Older patients' risk factors included stroke, administration of antibiotics, history of previous hospital admission within one month, and cancer. While young adults receiving two antibiotics were at greater risk of having CDI. 132 COVID-19 patients with diarrhea were identified and 7 (5%) of them were CDI positive. Conclusions: Investigating the risk factors of CDI in different age groups, including COVID-19 patients, is a crucial step to developing a risk-based prophylactic strategy to reduce the cost and burden on the healthcare system.