Hemorrhagic cystitis (HC) is one of the important complications threatened the safety of bone marrow transplantation (BMT). Early and late-onset HC with low to high severity have been seen in BMT patients. Different risk factors including: host factors, donor related factors and environmental factors have role in HC grading and presentation. In this research we tried to study the accurate role of these factors in HC related clinical complications in BMT recipients. In this cohort and retrospective investigation, for study of HC risk factors, the clinical and laboratory data of 283 transplanted patients between years: 1372-1385 were reviewed. Some of these patients received myeloablative regimen including busulfan and cyclophosphamide with or without etoposide. Other recipients received non myeloablative regimen including: fludarabin, cyclophosphamide and anti-thymocyte globulin. For prevention of GVHD, cyclosporine and prednisolone with or without methotrexate were used. HC prophylaxis was done by bladder irrigation or using mesna and hyper hydration. The collected results were statistically analyzed by SPSS soft ware. Results: Some of these results are presented as follow: HC was seen in 120 patients (42/4 %) including: early-onset in 47 (39/2%) and late-onset in 73 patients (60/8%). One to four grades of GVHD was seen respectively in 39 (32/5%), 43 (35/8%), 26 (21/6%) and 11(9/1%) transplant patients. The most cases with early-onset of HC was detected in donor-recipient sex mismatching (P=0/086). Significant correlations were detected between late onset of HC with use of bone marrow as a source of stem cells (P=0/001) and with class II and III of thalassemia as an underlying disease of BMT recipients (P=0/019). Receiving both cyclophosphamide and busulfan or ATG as transplant conditioning regimen increased the risk of late-onset of HC (P=0/001, p=0/073), respectively. Allogeneic transplant, GVHD symptoms and using prednisolone and cyclosporine as prophylaxis and treatment of GVHD increased the risk of late-onset and severity of HC presentation. Significant relationship was diagnosed between lower grades and late-onset of HC with anti-human cytomegalovirus ganciclovir and IVIg therapy (P=0/002). In conclusion, the results of this study showed that allogeneic transplant, donor-recipient sex match, bone marrow as a source of stem cell, class II & III of thalassemia as an underlying disease, use of busulfan and cyclophosphamide and ATG in conditioning regimen, GVHD symptoms, use of prednisolone and cyclosporine as prophylaxis and treatment of GVHD, and gancyclovir and IVIg as antiviral treatment have significant role in increasing the incidence and severity of HC clinical symptoms in BMT patients.