Abstract: OBJECTIVE To explore the risk factors of Clostridium difficile infection (CDI) among mechanically ventilated patients and to describe the influence of CDI on the outcomes of these patients. METHODS A total of 577 mechanically ventilated patients were retrospectively reviewed from Apr. 2014 to Apr. 2016, and were divided into CDI group (57 cases) and non-CDI group (523 cases). The risk factors of CDI infection in mechanically ventilated patients were analyzed, and the differences of survival rates between the two groups were compared. RESULTS The incidence of CDI in mechanically ventilated patients was 9.36%. There were no significantly differences between these two groups in gender, disease classification and the majority of concomitants. The CDI infection rates were high in patients with age ≥70 years, high APACHEⅡscore when admitted into ICU, long length of hospital and ICU stays and mechanically ventilated days (all P<0.05). Logistic multivariate regression analysis showed that CDI risk factors included age, APACHE Ⅱ score when admitted into the ICU, the use of antacids and the use of antimicrobial agents (≥ 3) before mechanical ventilation, and there was no statistically significant difference in survival rates within 30 days of admission between mechanical ventilation CDI infection and non-infection patients. CONCLUSION CDI is quite popular in mechanically ventilated patients, and can prolong hospital stays, ICU stays and mechanically ventilated days. Familiarity with CDI risk factors may help to reduce CDI infection rates.