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Clostridium difficile is the main infectious cause of antibiotic associated diarrhea (AAD). The objective of this study was to determine the frequency of C. difficile AAD in hospitalized patients. We searched MEDLINE (Pubmed), Embase, Web of Science and Cochrane library for subject headings and text words related to C. difficile AAD. Studies that investigated the prevalence or frequency of C. difficile AAD in health care settings were considered eligible. Using a random-effects model, data obtained from the identified studies were combined. Of the 2464 citations identified, twenty studies (5496 patients) met the inclusion criteria of the present study. Pooling all studies, the frequency of C. difficile among AAD patients was 20.0% (95% CI 13.0–28.0). The most frequently used antibiotics in health care settings were the following: Clindamycin, fluoroquinolones and cephalosporins. The current systematic review …