Clostridium difficile (pronunciation below) (from the Greek kloster (κλωστήρ), spindle, and Latin difficile, difficult), also known as "CDF/cdf", or "C. diff", is a species of Gram-positive bacteria of the genus Clostridium that causes severe diarrhoea and other intestinal disease when competing bacteria in the gut flora have been wiped out by antibiotics.

Clostridia are anaerobic, spore-forming rods (bacilli).C. difficile is the most serious cause of antibiotic-associated diarrhea (AAD) and can lead to pseudomembranous colitis, a severe inflammation of the colon, often resulting from eradication of the normal gut flora by antibiotics.

In a very small percentage of the adult population, C. difficile bacteria naturally reside in the gut. Other people accidentally ingest spores of the bacteria while they are patients in a hospital, nursing home, or similar facility. When the bacteria are in a colon in which the normal gut flora has been destroyed (usually after a broad-spectrum antibiotic such as clindamycin has been used), the gut becomes overrun with C. difficile. This overpopulation is harmful because the bacteria release toxins that can cause bloating and diarrhea, with abdominal pain, which may become severe. C. difficile infections are the most common cause of pseudomembranous colitis, and in rare cases this can progress to toxic megacolon, which can be life-threatening.