: Clostridium difficile (CD) is often classified as a healthcare-associated infection (HAI) and a hospital-acquired condition (HAC) in the hospital setting. However, pediatric oncology patients comprise a significant portion of Clostridium difficile infections (CDI), with hematopoietic stem cell transplant (HSCT) recipients constituting a major subset of this group due to unique, non-modifiable risk factors. We evaluated patterns of clostridium difficile infections at our institution to provide an accurate evaluation of the vulnerability of pediatric oncology and HSCT patients to clostridium difficile infections in comparison to the general pediatric population and underscore the non-tenability of classifying clostridium difficile infections as a hospital-acquired condition in HSCT patients. : Single-center retrospective review of all clostridium difficile stool tests performed over an 11-year period; data analyzed and statistical comparisons performed between patient groups. : 5271 total samples were obtained during the study time period from 3127 patients. At least one positive test result was found in 18.6% of patients. Oncology and HSCT patients (38.2%) were more likely to have a positive test result than hematology (17.5%) and other patients (16.8%) ( < 0.001). Sixty-percent of patients who underwent HSCT were tested during this time frame. Of those, 39.3% had a positive test result and 48.5% of those patients went on to have a subsequent infection that met the criteria to be defined as recurrent. : The high incidence rate and frequency of recurrence underscores the current near-inevitable nature of clostridium difficile infections in oncology and HSCT patients. We conclude that a blanket designation of clostridium difficile infections as an hospital-acquired condition is therefore questionable in this population.