The missense variant S180L in TIRAP (Toll-interleukin-1 receptor domain-containing adaptor protein) gene is implicated in attenuating TLRs signal transaction and may affect individual response to Mycobacterium tuberculosis infection. Several studies investigated the association between TIRAP S180L and risk of tuberculosis (TB), but the results were controversial. In this study, we quantitatively synthesized nine studies relevant to the association between TIRAP S180L polymorphism and TB risk with total 6584 TB cases and 7294 controls using meta-analysis. We found that the variant allele Leu180 and heterozygous genotype Ser/Leu were not significantly associated with risk of TB (allelic OR = 0.99, 95%CI: 0.88–1.11; Ser/Leu vs Ser/Ser: OR = 0.99, 95%CI: 0.87–1.13) with heterogeneity P values > 0.05. In subgroup analysis, none of the significant associations were observed for S180L and TB risk in Africans (allelic OR = 0.58, 95%CI: 0.29–1.61; heterozygous OR = 0.65, 95%CI: 0.32–1.32) or Asians (allelic OR = 1.30, 95%CI: 0.97–1.74; heterozygous OR = 1.17, 95%CI: 0.84–1.65) or risk of pulmonary tuberculosis (PTB) (allelic OR = 0.92, 95%CI: 0.69–1.22; heterozygous OR = 0.98, 95%CI: 0.86–1.12). This meta-analysis indicates that TIRAP S180L polymorphism is unlikely to substantially contribute to TB susceptibility.