The heterodimeric transporter associated with antigen processing (TAP) gene loci is known to play a vital role in immune surveillance. We investigated a possible association of gene polymorphisms both in TAP1 and TAP2 in a cohort of clinically classified leprosy patients (n = 222) and in ethnically matched controls (n = 223). The TAP1 and TAP2 genes were genotyped for four single nucleotide polymorphisms TAP1 (rs1057141 Iso333Val and rs1135216 Asp637Gly) and TAP2 (rs2228396 Ala565Thr and rs241447 Ala665Thr) by direct sequencing and ARMS-PCR. The minor allele of TAP1 637G contributes to an increased risk to leprosy compared to controls (OR: 1.68, 95% CI 1.2–2.36, P = 0.0057). An increased risk for the variant minor allele of the TAP1 637G to multibacillary (BL + LL) or paucibacillary (BT + TT) infections was also observed [multibacillary vs. controls (OR: 1.56, 95% CI 1.07–2.28, P = 0.054); paucibacillary vs. controls (OR: 1.92, 95% CI 1.21–3.01, P = 0.013)]. In the dominant model, the genotypes of the TAP1 rs1135216AG + GG additionally contributed to an increased risk. Overall our findings demonstrate that the TAP1 gene variant (rs1135216 Asp637Gly) influences the susceptibility to clinically classified leprosy patients in Indian population