A hallmark of the diagnosis of chronic obstructive pulmonary disease (COPD) is the measurement of post-bronchodilator (post-BD) airflow obstruction (AO) by spirometry, but spirometry is not enough for the provision of a clinical diagnosis. In the majority of previous epidemiological studies, COPD diagnosis has been based on spirometry and a few clinical characteristics. The aim of our study was to identify outcomes in patients newly diagnosed with airflow obstruction (AO) based on a diagnostic work-up conducted as part of a population-based cross-sectional study in North-Western Russia. Spirometry was performed before (pre-BD) and after BD administration, and AO was defined using the FEV1/FVC <0.70 and FEV1/FVC <lower limit of normal cut-off values. Relevant symptoms were recorded. Participants with AO identified at baseline were then examined by a pulmonologist, including a clinical examination and second spirometry with BD test. Of the 102 participants with post-BD AO in the initial assessment, only 60.8% still had AO identified at the second examination; among these patients, the following final diagnoses were reported: COPD (n = 41), asthma (n = 5), asthma-COPD overlap syndrome (ACOS) (n = 4) and likely ACOS (n = 5). Of the 65 participants with pre-BD AO, 23.1% had post-BD AO at the second assessment, and these patients had been diagnosed with COPD (n = 12), asthma (n = 1), ACOS (n = 1), likely ACOS (n = 1). Serial spirometric assessments complemented by a comprehensive clinical evaluation are recommended in new epidemiological studies.