Background: Clostridium difficile infection (CDI) is a common cause of nosocomial diarrhoea. People in the general community are not usually considered to be at risk of CDI. CDI is associated with a high risk of morbidity and mortality. The risk of severity is defined by the Clostridium Severity Index (CSI). Methods: The cases of 136 adult patients with CDI treated at the University Hospital of Tours, France between 2008 and 2012 are described. This was a retrospective study. Results: Among the 136 patients included, 62 were men and 74 were women. Their median age was 64.4 years (range 18–97 years). Twenty-six of the 136 (19%) cases were community-acquired (CA) and 110 (81%) were healthcare-acquired (HCA). The major risk factors for both groups were long-term treatment with proton pump inhibitors (54% of CA, 53% of HCA patients) and antibiotic treatment within the 2.5 months preceding the CDI (50% of CA, 91% of HCA). The CSI was higher in the CA-CDI group (1.56) than in the HCA-CDI group (1.39). Intensive care was required for 8% of CA-CDI and 16.5% of HCA-CDI patients. Conclusions: CDI can cause community-acquired diarrhoea, and CA-CDI may be more severe than HCA-CDI. Prospective studies of CDI involving people from the general community without risk factors are required to confirm this observation.