Background: Prostatic epithelial cells synthesize the active form of vitamin D (1, 25-dihydroxyvitamin D3), which participates in regulating prostate growth. Calcitriol, a synthetic form of vitamin D3, exhibits antiproliferative and pro-differentiation activities in prostate cancer. The function of 1, 25-dihydroxyvitamin D3 is mediated by its binding to vitamin D receptor (VDR). VDR forms a heterodimer, typically with retinoid X receptor, to regulate vitamin D target genes. We evaluated the relationship between VDR polymorphisms and clinical characteristics associated with prostate cancer risk and prognosis among Egyptian men. Methods: This case-control study included two groups of patients: group A, control group of 50 apparently healthy males; group B: 50 subjects newly diagnosed with prostate cancer. Results: Patients with prostate cancer and controls showed significantly different genotypes (P < 0.001). Furthermore, prostate-specific antigen levels were significantly higher in C allele carriers than in A allele carriers among patients with prostate cancer (P < 0.001). Finally, T stage and the VDR Apa1 C/A polymorphism were significantly associated (P < 0.04). Conclusions: The VDR Apa1 C/A polymorphism may be a diagnostic and prognostic marker for prostate cancer in Egyptian men.