Clostridium difficile infection (CDI) has become the leading cause of hospital acquired nosocomial diarrhea worldwide. The prolonged hospital stays associated with CDI has enormous impact on the healthcare systems in terms of costs and patient outcomes. While treatment of CDI is an important area for ongoing research, prevention efforts will need to be enhanced to interrupt CDI transmission. Given the current efforts for the development of an anti-CDI vaccine, research to evaluate vaccine and its impact along with the existing intervention measures is a key component of the healthcare system approaches to combating CDI. We develop a state-of-the-art simulation model to assess the effectiveness of measures currently in practice, including