Clostridium difficile may refer to:
- Clostridium difficile (bacteria), also known as C. difficile, C. diff, or sometimes CDF/cdf, an older name for Clostridioides difficile, a species of Gram-positive spore-forming bacteria
- Clostridium difficile infection or colitis (inflammation of the large intestine) resulting from infection with Clostridioides difficile bacteria
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