Clostridium difficile is the most common cause of infectious nosocomial diarrhea among adults in developed countries. Nonalcoholic fatty liver disease (NAFLD) is considered the most common chronic liver disease. Our goal was to assess whether there is any association between Clostridium difficile- associated diarrhea (CDAD) and NAFLD.We conducted a retrospective study of patients admitted with CDAD at Baruch Padeh Medical Center, Poria, Israel. Data on demographic characteristics, clinical signs, underlying conditions, presence of fatty liver based on CT/US imaging, and several risk factors for CDI were collected. The control group included patients with diarrhea who were negative for CDT and had been hospitalized during the same period. The controls were matched for age (± 5 years) , and gender.115/164 patients with CDAD met the inclusion criteria.The control group was consisted of 115 hospitalized patients with non-CDAD. The mean age of all the participants (230) was 69.57± 18 years. NAFLD was found in 76/115 (66%) patients with CDAD vs. 35/115 (30.4%) in the control group, P<0.001. Moreover, we found significant associations between CDAD group and metabolic syndrome, prior use of antibiotic in the last 3 months, NAFLD and high serum levels of C-reactive protein. Multivariate analysis showed that NAFLD, odds ratio (OR) 1.51, 95% confidence interval (CI): 1.2-1.95, P=0.05 was significantly associated with CDAD.This retrospective study showed that NAFLD is associated with the risk of CDAD. Moreover, metabolic syndrome and high serum levels of CRP were significantly associated with the risk of CDAD.