Some polymorphisms of the <i>VDR</i> gene, such as <i>Bsm</i>I (G>A rs1544410)<i>, Apa</i>I (G>T rs7975232), and <i>Taq</i>I (T>C rs731236) could affect its stability and mRNA transcription activity, while <i>Fok</i>I T>C (rs2228570) gives a truncated protein with three fewer amino acids and more efficiency in binding vitamin D. This study evaluated these four polymorphisms in the immunopathogenesis of leprosy in 404 patients and 432 control individuals without chronic or infectious disease in southern Brazil.