Background: Post-transplant lymphoproliferative disorder (PTLD) is a lymphoplasmacytic proliferative disorder in the setting of hematopoietic stem cells and solid organ transplants. PTLD is divided into nondestructive, polymorphic, monomorphic, and classical Hodgkin lymphoma subtypes. Most cases of PTLDs are Epstein-Barr virus (EBV) related (two third of the cases), and most are of B cell (80-85%) origin. The polymorphic PTLD subtype can be locally destructive and show malignant features. Treatment for PTLD includes a reduction in immunosuppression, surgery, cytotoxic chemotherapy and/or immunotherapy, anti-viral agents, and/or radiation. The aim of this study was to examine the demographic factors and treatment modalities that influence survival in patients with polymorphic PTLD.Methods: About 332 cases of polymorphic PTLD were identified from 2000 to 2018 using the Surveillance, Epidemiology, and End Results (SEER) database.Results: The median age of the patients was found to be 44 years. The most common age groups were between the ages of 1-19 years (n=100. 30.1%) and 60-69 years (n=70. 21.1%). The majority of cases in this cohort underwent systemic (cytotoxic chemo and/or immuno) therapy only (n=137, 41.3%), while 129 (38.9%) cases did not undergo any treatment. The overall five-year observed survival was 54.6% (95% confidence interval (CI), 51.1 - 58.1). One-year and five-year survival with systemic therapy was 63.8% (95% CI, 59.6 - 68.0) and 52.5% (95% CI, 47.7 - 57.3), respectively. The one-year and five-year survival with surgery was 87.3% (95% CI, 81.2-93.4) and 60.8% (95% CI., 42.2 - 79.4), respectively. The one-year and five-year without therapy were 67.6% (95% CI, 63.2-72.0) and 49.6% (95% CI, 43.5-55.7), respectively. Univariate analysis revealed that surgery alone (hazard ratio (HR) 0.386 (0.170-0.879), p = 0.023) was a positive predictor of survival. Race and sex were not predictors of survival, although age >55 years was a negative predictor for survival (HR 1.128 (1.139-1.346), p <0.001).Conclusion: Polymorphic PTLD is a destructive complication of organ transplantation that is usually associated with EBV positivity. We found that it most often presents in the pediatric age group, and its occurrence in those older than 55 years was associated with a worse prognosis. Treatment with surgery alone is associated with improved outcomes and should be considered in addition to a reduction in immunosuppression in cases of polymorphic PTLD.