BACKGROUND/AIM: Vitamin D receptor (VDR) is present in numerous cellular pathways and it has been suggested that VDR genetic variants influence individual susceptibility to prostate cancer. Also, analyses of single nucleotide polymorphisms (SNPs) in VDR revealed ethnicity-associated polymorphisms. The aim of this study was to identify VDR SNPs in African American men with and without prostate cancer. MATERIALS AND METHODS: The entire VDR gene was screened for germline mutations in a case-control study by denaturing high performance liquid chromatography and DNA sequencing. Logistic regression was used to estimate the association of SNPs, age, family history, and Gleason score with prostate cancer risk. RESULTS: Six SNPs in the non-coding regions, and one SNP in the coding region, were detected. SNP 1 (c.278-69G>A) and SNP 4 (c.907+75C>T) have not been previously reported. SNP 4 had a significant protective effect (β=-0.6, p<0.05); whereas, SNP 7 (rs7975232) showed an increase association with prostate cancer risk and high Gleason score (β=0.32, p<0.05). SNP 4, SNP 7 and age were better predictors of prostate cancer risk than family history with a high degree of sensitivity (74.7%) and specificity (92.4%). CONCLUSION: SNP 4 and SNP 7 could be promising markers for prediction of reduced or increased prostate cancer risk, respectively.