Background: Hematopoietic stem cell transplant (HSCT) recipients are at a higher risk of clostridium difficile infection (CDI). The incidence of CDI in allogenic SCT recipients has been shown to be about 2-fold compared to autologous SCT recipients in certain studies. These differences can be attributed to myeloablative chemotherapy and increased duration of immunosuppression in allogenic SCT patients. In this study we evaluate the impact of CDI on in-hospital outcomes in these two groups of patients. Methods: We included all patients with a prior diagnosis or a procedure code for HSCT and CDI using ICD-10 codes from National Inpatient Sample 2016-2019. Patients were stratified into two groups based on the presence or absence of autologous stem cell transfusion. Information was collected regarding patient demographics, Charlson comorbidities, resource utilization (LOS and total hospitalization charges), and outcomes. The outcomes included sepsis, shock, acute kidney injury, ICU admission, and in-hospital mortality. The differences in outcomes between the two groups were studied. Results: The incidence of CDI in autologous stem cell transplant recipients was lower compared to the allogenic HSCT group (5.1% vs. 6.1%, p-0.003). 7,605 patients were included in the study. Of them, 2,460 (32.25%) patients had autologous stem cell transplantation, while the remaining had allogenic stem cell transfusion. A higher proportion of patients in the autologous stem cell transplant group were males (60.7% vs. 54.32%), and patients aged 45-64 years (55.7% vs. 46.4%). Patients who received autologous stem cell transplants had a lower incidence of death (1.6% vs. 7.8%, p < 0.001), sepsis (17.28% vs. 28.18%, p- < 0.001), shock (4.7% vs. 12%, p < 0.001), AKI (15% vs. 31.6%, p < 0.001) and ICU admissions (5.7% vs. 10.7%, p- < 0.001). There was no significant difference in the length of stay between the two groups (21.30 days vs 22.97 days). Patients in the autologous stem cell transplant group had lower hospitalization charges ($318,072.3 vs $402,281.5, p < 0.001) than the allogenic group. Conclusions: Like prior studies, our study is compatible with the lower incidence of CDI in autologous SCT recipients. Our study also suggested a lower in-hospital mortality and better outcomes compared to patients with allogeneic stem cell transplants. Resource utilization was also noted to be lower in autologous stem cell transplant patients. Further research should be conducted to explain the differences and to allow physicians to provide timely treatments to prevent worse outcomes.