The impact of clostridium difficile infection (CDI) on patients’ health and hospitals’ cost is significant. Currently CDI is recognized as an increasingly important pathogen in children with increasing incidence among pediatric patients. Data is scarce on the incidence and risk factors of CDI in Saudi Arabia, especially in pediatric oncology population. In this study, we report the first outbreak of CDI in pediatric hematology-oncology ward in Saudi Arabia and describe the associated risk factors for CDI.