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Background: The aim of this study was to determine the pathologic causes of renal allograft failure in transplant nephrectomy specimens. Materials and Methods: In this cross-sectional study performed in the referral transplant center of Isfahan, Iran, medical files of all patients who underwent nephrectomy in 2008–2013 were studied. Age at transplantation, sex, donor's characteristics, causes of primary renal failure, duration of allograft function, and pathologic reasons of nephrectomy were extracted. Slides of nephrectomy biopsies were evaluated. Data were analyzed using SPSS. Results: Medical files of 39 individuals (male: 56.4%; mean age: 35.1 ± 16.0 years) were evaluated. The main disease of patients was hypertension (17.9%), and most cases (64.1%) were nephrectomized < 6 months posttransplantation. Renal vein thrombosis (RVT) (51.3%) and T-cell-mediated rejection (TCMR) (41.0%) were the most prevalent causes of transplanted nephrectomy. Cause of primary renal failure was correlated to nephrectomy result (P = 0.04). TCMR was the only pathologic finding in all of patients nephrectomized >2 years posttransplantation. There were 14 cases in which biopsy results showed a relationship between primary disease of patients and pathologic assessment of allograft (P = 0.04). A significant relationship between transplantation-nephrectomy interval and both the nephrectomy result and histopathologic result existed (P < 0.0001). A relationship between primary allograft biopsy appearance and further assessment of nephrectomized specimen (P < 0.001) existed as well. Conclusion: The most pathologic diagnoses of nephrectomy in a period of less than and more than 6 months posttransplantation were RVT and TCMR, respectively. Early obtained allograft protocol biopsy is suggested, which leads to better diagnosis of allograft failure.