Clostridium difficile is an anaerobic gram-positive bacillus, capable of forming spores and toxins, transmitted to humans by the faecal-oral route C. difficile infection (CDI) is recognized as a typical cause of healthcare-associated infections (HAIs) and contributes to a significant proportion of morbidity and mortality of hospitalized patients. C. difficile culture and toxin examinations are still minimal in many hospitals in various Asian countries. As a result, reports of C. difficile in Asia are still rare, while reports of cases of CDI in Indonesia are still rare. Several risk factors including advanced age, antibiotic exposure, and hospitalization are strongly associated with CDI. C. difficile has the ability to colonize the large intestine, then release exotoxin proteins (TcdA, TcdB) causing colitis in people with risk factors. A diagnosis of suspected C. difficile infection in a patient with diarrhea without a clear alternative explanation, with relevant risk factors (including long antibiotic consumption, hospitalization events, and elderly age), was then performed microbiological examination to carry out proper management and control of infection. This study aims to review C. difficile virulence factors as the cause of antibiotic-associated diarrhea.