Background: Hyperacute graft versus host disease (GVHD) after allogenic stem cell transplantation (SCT) has adverse outcomes with increased rates of chronic GVHD and relapse. GVHD risks include mismatched related or matched unrelated donors, myeloablative conditioning, heavy pretreatment, and donor-recipient sex mismatch. Clostridium difficile infection (CDI) is a leading cause of diarrhea in immunocompromised patients. Proposed microbiome effect on immunity and GVHD in allogenic SCT recipients prompts concern of microbiome modulation from CDI and antibiotics inciting GVDH. Methods: National Inpatient Sample database 2014 for hospitalizations with allogeneic SCT in patients ≥18yo. Characteristics (age, sex, race, insurance, graft source, hospital type, region, comorbidities) were compared for hospitalizations with and without CDI. Primary outcome was the difference in the incidence of GVHD during the transplant hospitalization between the 2 groups. Other outcomes were mortality, length of stay and hospital charges. Chi-square, t-test, and multivariate logistic regression utilized. Results: Of 6210 patients with allogenic SCT, 745 (12%) had CDI during the transplant hospitalization. In transplanted patients without CDI the average age was 55yo, 43.9% female, 69.5% Caucasian (C), 7.1% African American (AA), 8.6% Hispanic (H), 32.1% had Medicare/Medicaid, 61.8% private insurance, 5.7% uninsured, 44.7% had hypertension, 13.7% had diabetes, graft source was 84.3% PBSC (peripheral blood stem cells), 11.3% bone marrow, and 4.4% cord blood. CDI group the average age was 52.5yo, 45.3% female, 73% C, 4.7% AA, 8.1% H, 25.7% had Medicare/Medicaid, 66.2% private insurance, 8.1% uninsured, 41.9% had hypertension, 10.1% had diabetes, graft source was 83.8% PBSC, 10.8% bone marrow, and 5.4% cord blood. 25.7% of patients with CDI developed GVHD during that hospitalization while 14.2% of patients without CDI developed GVHD during the hospital stay (OR 2.1, p < 0.001 multivariate analysis). GVHD during the hospitalization had no difference in length of stay (p = 0.32), total cost of stay (p = 0.50) or same hospitalization mortality (p = 0.94). Conclusions: Allogeneic SCT patients with CDI develop GVHD on the same hospitalization at significantly higher rates than patients without CDI. This is true after controlling for age, sex, race, insurance, comorbidities, graft source, hospital location, and type of institution. Despite known associations of early evidence of GVHD on relapse, overall mortality was not different between the two groups.