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Background: Multiple sclerosis (MS) is an autoimmune disease which demyelinates the central nervous system. Vitamin D, is a potential environmental factor which influences this disease. The majority of the biological activities of the polymorphism forms of vitamin D are done through its receptor gene (VDRG). The aim of this study was to examine the relationship between BsmI polymorphisms in VDRG and the incidence of MS. Materials and Methods: In this case-control study, the BsmI polymorphism in the VDRG was studied in 80 Iranian MS patients and 50 healthy controls of the same genetic background and age through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method Results: There was a significant difference in the frequency of BsmI VDRG polymorphism genotypes between MS patients and controls (P=0.023). Conclusion: This study indicated that the VDRG BsmI polymorphism is associated with MS in this population.