Abstract : Vitamin D is considered to be of high importance in the bone’s mineralization. The Vitamin D receptors genetic polymorphism might be associated with the status of vitamin D besides the bone mineral density that have been characteristic features related to the Beta thalassemia major (β-TM) patients. The presented work has been conducted on 100 patients with β-TM in addition to 100 healthy age and sex matched controls for the purpose of evaluating the impact related to VDR polymorphisms on the levels of vitamin D in addition to the bone mass density (BMD). Furthermore, the serum biochemical markers like alkaline phosphates, inorganic phosphorus, ionized calcium as well as vitamin D have been evaluated. The VDR genetic polymorphisms (FokI and Bsml) have been genotyped through the polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR). Also, the BMD has been evaluated through X-ray densitometry (DEXA) related to lumbar spine and femoral neck. The results that are related to β-TM patients showed considerable deficiency of vitamin D, also the BMD Z score has been considerably low in the β-TM patients when compared to the non-thalassemic subject (p < 0.001). Osteopenia as well as osteoporosis related to lumbar spines and femoral neck have been indicated in the β-TM patients. Furthermore, the BsmI AG in addition to the FokI CT genotypic polymorphisms have been considerably related to low vitamin D as well as BMD Z score. The low BMD has been widespread in the patients experiencing β-TM. Also, the BsmI AG as well as the FokI CT genotypic polymorphisms related to the VDR might be specified as risk factors for the include regarding osteoporosis in such β-TM patients