Vascular endothelial growth factor (VEGF) is a regulator of angiogenesis and a mediator of sex steroid-induced cell growth and differentiation. We aimed to investigate if VEGF gene 5'-UTR -460 polymorphism could be used as markers of susceptibility in leiomyoma. Women were divided into two groups: (1) leiomyoma (n = 159); (2) nonleiomyoma groups (n = 131). VEGF gene -460 polymorphism were detected by polymerase chain reaction and BstUI restriction enzyme analysis. Genotypes and allelic frequencies between both groups were compared. We noted that the proportions of different VEGF polymorphisms in both groups were significantly different. Proportions of cuttable (C) homozygote/heterozygote/uncuttable (T) homozygote for VEGF in both groups were: (1) 0/32/68% and (2) 0/63/37%. Higher percentage of T homozygote and T allele presented in the leiomyoma population. Proportions of C/T alleles in both groups were: (1) 16/84% and (2) 32/68%. We concluded that T homozygotes and T allele of VEGF gene -460 polymorphism are associated with higher risk of leiomyoma development. Heterozygotes and C allele are related with lower risk of leiomyoma formation. VEGF gene polymorphism likely contributes to the pathogenesis of leiomyoma.