Three-dimensional airway analysis, using high-resolution computed tomography (CT), has only recently become a reality for studying airway dimensions and remodeling in chronic obstructive pulmonary disease (COPD). Herein, we show how we validated our new software using phantoms, and how we applied this software to a clinical study. Using this software, we have demonstrated that the percentage of predicted forced expiratory volume in 1 second in patients with COPD correlated highly with airway luminal area and, to a lesser extent, with percentage wall thickening (WA%) from the 3rd to the 6th generation of both the apical upper bronchus (B1) and the anterior lower bronchus (B8). More importantly, we also showed that correlation coefficients improved with decreasing airway size in both airways. In the near future, with further advances in both software and CT technology, this kind of approach will become even more attractive. Using this readily accessible and relatively noninvasive technique, we are conducting a longitudinal study of subjects recruited for the Hokkaido COPD cohort study. Potential problems in the application of three-dimensional airway analysis to such longitudinal follow-up studies and/or large-scale multicenter studies are also discussed.