The purpose of this study was to investigate the TaqI vitamin D receptor (VDR) polymorphism in both Japanese prostate cancer patients and Japanese noncancer controls in order to determine if an association exists between VDR genotype with clinical and pathological risk of prostate cancer patients. This study involved 115 patients with prostate cancer and 133 male age-matched noncancer controls genotyped for a previously described TaqI restriction fragment length polymorphism (RFLP) at codon 352 in exon 9 of the VDR gene. Products were digested into T allele or t allele according to the absence or presence of TaqI restriction site with individuals being classified as TT, Tt, or tt. The genotype tt was higher among the control group (6.0%) compared to the patients with prostate cancer (1.8%), but not so (OR=0.28; 95%o CI, 0.06-1.33; p=0.081). In addition, the genotype TT was statistically higher among patients with locally advanced or metastatic disease (T3/T4/NI/M1) compared to controls (OR=2.52; 95%o CI, 1.21-5.27; p=0.009). Lastly, the genotype TT was statistically higher among patients with poorly differentiated adenocarcinoma compared to controls (OR=5.38; 95%o CI, 1.57-18.50; p=0.002). These data demonstrate that VDR genotype plays an important role in determining the risk of more clinically advanced and pathologically aggressive prostate cancer which is associated with a higher mortality rate in Japanese men.