IL-17A is an important pro-inflammatory cytokine involved in the inflammatory response in chronic obstructive pulmonary disease (COPD). To evaluate the role played by single nucleotide polymorphisms of IL17A and protein levels in susceptibility to COPD, 1,807 subjects were included in a case-control study; 436 had COPD related to tobacco smoking (COPD-S) and 190 had COPD related to biomass burning (COPD-BB). Six hundred fifty-seven smokers without COPD (SWOC) and 183 biomass burning-exposed subjects (BBES) served as the respective control groups. The CC genotype and C allele of rs8193036 were associated with COPD (COPD-S vs. SWOC: p < 0.05; OR = 3.01, and OR = 1.28, respectively), as well as a recessive model (p < 0.01; OR = 2.91). Significant differences in serum levels were identified between COPD-S vs. SWOC, COPD-S vs. COPD-BB, and SWOC vs. BBES (p < 0.01). By comparing genotypes in the COPD-BB group TT vs. CC and TC vs. CC (p < 0.05), we found lower levels for the CC genotype. Logistic regression analysis by co-variables was performed, keeping the associations between COPD-S vs. SWOC with both polymorphisms evaluated (p < 0.05), as well as in COPD-BB vs. BBES but with a reduced risk of exacerbation (p < 0.05). In conclusion, polymorphisms in IL17A are associated with COPD. Serum levels of IL-17A were higher in smokers with and without COPD.