RATIONALE: Current assessment of COPD relies extensively on the use of spirometry, an effort-dependent maneuver. Impulse oscillometry (IOS) is a non-volitional way to measure respiratory system mechanics, but its relationship to structural and functional measurements in large groups of patients with COPD is not clear. OBJECTIVES: We evaluated the ability of IOS to detect and stage COPD severity in the prospective ECLIPSE cohort of COPD patients defined spirometrically, and contrasted with smoking and non-smoking healthy subjects. Additionally, we assessed whether IOS relates to extent of CT-defined emphysema. METHODS: We measured lung impedance with IOS in healthy non-smokers (n = 233), healthy former smokers (n = 322) or patients with COPD (n = 2054) and related these parameters with spirometry and areas of low attenuation in lung CT. MEASUREMENTS AND MAIN RESULTS: In healthy control subjects, IOS demonstrated good repeatability over 3 months. In the COPD group, respiratory system impedance was worse compared with controls as was frequency dependence of resistance, which related to GOLD stage. However, 29-86% of the COPD subjects had values that fell within the 90% confidence interval of several parameters of the healthy non-smokers. Although mean values for impedance parameters and CT indices worsened as GOLD severity increased, actual correlations between them were poor (r </= 0.16). CONCLUSIONS: IOS can be reliably used in large cohorts of subjects to assess respiratory system impedance. Cross-sectional data suggest that it may have limited usefulness in evaluating the degree of pathologic disease, whereas its role in assessing disease progression in COPD currently remains undefined.