Bronchodilator responsiveness (BDR) is prevalent in COPD, but its clinical implications remain unclear. We explored the significance of BDR, defined by post-bronchodilator change in FEV (BDR) as a measure reflecting the change in flow and in FVC (BDR) reflecting the change in volume.We analyzed 2974 participants from a multicenter observational study designed to identify varying COPD phenotypes (SPIROMICS). We evaluated the association of BDR with baseline clinical characteristics, rate of prospective exacerbations and mortality using negative binomial regression and Cox proportional hazards models.A majority of COPD participants exhibited BDR (52.7%). BDR occurred more often in earlier stages of COPD, while BDR occurred more frequently in more advanced disease. When defined by increases in either FEV or FVC, BDR was associated with a self-reported history of asthma, but not with blood eosinophil counts. BDR was more prevalent in subjects with greater emphysema and small airway disease on CT. In a univariate analysis, BDR was associated with increased exacerbations and mortality, although no significance was found in a model adjusted for post-bronchodilator FEV.With advanced airflow obstruction in COPD, BDR is more prevalent in comparison to BDR and correlates with the extent of emphysema and degree of small airway disease. Since these associations appear to be related to the impairment of FEV, BDR itself does not define a distinct phenotype nor can it be more predictive of outcomes, but it can offer additional insights into the pathophysiologic mechanism in advanced COPD.ClinicalTrials.gov: NCT01969344T4.