Clostridium difficile causes diarrhea that ranges from a benign, self-limiting antibiotic use-associated disease to a life-threatening pseudomembranous colitis. Clostridium difficile has rarely been isolated in extraintestinal infections. Our objective was to characterize clinical features and risk factors of these infections. METHODS Extraintestinal C. difficile infections (CDIs) were searched for in an electronic database of all C. difficile-positive isolates found during a 10-year period. The medical records were reviewed retrospectively. Disease severity and comorbidities of the patients were evaluated using Horn disease severity and Charlson comorbidity indexes. Extraintestinal CDI was found in 31 patients who comprised 0.17% of all CDIs. Two patients had bacteremic infections, 4 had abdominal infections without any prior surgery, 7 had abdominal infections after surgery, 4 had perianal abscesses, 13 had wound infections, and 1 had C. difficile in a urinary catheter. In most cases (85%), C. difficile was isolated together with other microbes. Most (81%) patients developed the infection when hospitalized and many had severe comorbidities. Sixteen (52%) had diarrhea. The 1-year mortality rate was 36% and it correlated with the severity of underlying diseases. Extraintestinal CDIs occur mainly in hospitalized patients with significant comorbidities. Extraintestinal CDIs in the abdominal area may result from either intestinal perforation after infection or after intestinal surgery. Wound infections may result from colonization by feces. Clostridium difficile may reach distant sites via bacteremia. Mortality in extraintestinal CDIs is associated with the severity of underlying diseases.