Abstract: Background and Objective: Clostridium difficile (C. diff) is the most frequent cause of hospital-acquired diarrhea. This study will characterize the demographics and outcome of Clostridium difficile infections (CDIs) in an Intensive Care Unit (ICU) population. Materials and Methods: Prospective, single-center study in a twelve-bed ICU in a tertiary hospital. Forty-two patients having diarrhea were investigated. Twenty-five with antibiotic-associated diarrhea (AAD) and the remaining seventeen with non-antibiotic-associated diarrhea (NAAD). As 15 healthy individuals in a control group were also studied. Three laboratory methods were used to diagnose toxigenic Clostridium difficile in stool samples: Clostridium difficile culture on cycloserine cefoxitin fructose agar, toxin A detection by a rapid immunoassay test and PCR for detection of Clostridium difficile toxin A and B genes. Results: Nine stool samples yielded positive results in at least one assay, eight (19.0%) were positive by culture, seven (16.6%) were positive according to the toxin A detection method and fifteen were positive according to PCR. One stool sample from the control subjects was positive by culture, but negative results were obtained from the other two assays (toxin A detection and PCR). The incidence of Clostridium difficile-Associated Disease (CDAD) using the three tested methods was estimated in the AAD group which was 34.2% and the incidence of CDAD in the NAAD group was 5.7%. Conclusion: In this work, a more severe form of the disease at the outset of diagnosis of infection, as indicated by a high SOFA score and age were independent predictors of morbidity within the ICU.