Clostridium difficile causes antibiotic-associated colitis; it colonizes the human intestinal tract after the normal gut flora has been altered by antibiotic therapy. It is one of the most common healthcare-associated infections and a significant cause of morbidity and mortality among older adult hospitalized patients. The clinical manifestations and diagnosis of C. difficile infection will be reviewed here. The treatment, pathophysiology, and epidemiology of this disorder are discussed separately. (See "Clostridium difficile in adults: Treatment" and "Clostridium difficile in adults: Epidemiology, microbiology, and pathophysiology".) CLINICAL MANIFESTATIONS — C. difficile infection can cause a spectrum of manifestations ranging from an asymptomatic carrier state to fulminant disease with toxic megacolon (table 1) [1,2]. The basis for this range of clinical manifestations is not fully understood but may be related to various host and pathogen factors. (See "Clostridium difficile in adults: Epidemiology, microbiology, and pathophysiology".) Diarrhea with colitis — Watery diarrhea is the cardinal symptom of C. difficile–associated diarrh