Aim: The main goal of the study was to determine the diagnostic value of exhaled breath temperature as a possible non-invasive marker of susceptibility to a cigarette smoke in smokers. Study design: The study was conducted as a part of a multicenter prospective cohort study in active smokers at risk for developing COPD. In the first phase subjects at risk for developing COPD were recruited through primary care. Recruited subjects were reviewed by a pulmonologist after 2-4 weeks according to the diagnostic protocol to rule out or confirm the diagnosis and the severity of COPD according to GOLD guidelines. In the second phase subjects without a diagnosis of COPD and those in GOLD stage 0 and I were reassessed after 2 years of follow-up. Subjects and methods: According to the inclusion criteria 333 active smokers were included and underwent a diagnostic workup: medical history along with comorbidities, physical examination, after which subjects filled The European Community Respiratory Health Survey II, St. George Respiratory Questionnaire and COPD Assessment Test, followed by laboratory tests, pulmonary function tests (screening spirometry using COPD6, spirometry with bronchodilation test, 6-minute walk test) and measurement of exhaled breath temperature before and after smoking a cigarette. Subjects (n=146) without a diagnosis of COPD and those in GOLD stage 0 and I were reassessed by a pulmonologist for the diagnosis and the severity of COPD after 2 years of follow-up. Results: Change in exhaled breath temperature after smoking a cigarette at initial assessment with a threshold value change of 0.2 °C had a sensitivity of 62.5%, specificity of 73.7%, PPV of 13.9% and NPV of 96.7% for differentiating subjects with a newly diagnosed COPD after 2 years of follow-up, and a sensitivity of 63.6 %, specificity of 73.7%, PPV of 18.4% and NPV of 95.6% for for differentiating subjects with a progression of disease. Change in exhaled breath temperature after smoking a cigarette was significantly different in all three categories of disease progression (newly diagnosed COPD; newly diagnosed COPD+severity progression; loss of postbronchodilator FEV1 >50 ml/yr) after 2 years of follow-up, and exhaled breath temperature before smoking was significantly different for two categories of disease progression (newly diagnosed COPD; newly diagnosed COPD+severity progression). The loss of lung function after 2 years was the largest in the group of patients with COPD GOLD I stage. Conclusion: Exhaled breath temperature could be used as one of the early markers of COPD in smokers at risk.