In conclusion, we here describe that (i) patients with active TB who smoke have a negative effect on radiological manifestations, sputum culture conversions in a dose-dependent manner, and treatment extension, (ii) tobacco smoke increases probability of false-negative IGRA results in active TB and LTBI patients due to decreased IFN-γ secretion, and (iii) IFN-γ response is affected by smoking being related with the pack-years consumption. The gene discussed is IFNG; the disease is tuberculosis.