Rationale: Oxygen-enhanced MR imaging (O₂-enhanced MRI) has been proposed as a useful tool for assessment of regional morphological and functional changes in chronic obstructive pulmonary disease (COPD). Objective: To prospectively and directly compare the efficacy of O₂-enhanced MRI and quantitative CT for smoking-related pulmonary functional loss assessment and clinical stage classification of smoking-related COPD. Methods: 160 smokers were classified into four age- and gender-matched groups by using the GOLD criteria for smokers: 'Smokers without COPD (n=40)', 'Mild COPD (n=40)', 'Moderate COPD (n=40)', 'Severe or Very Severe COPD (n=40)'. All smokers underwent O₂-enhanced MRI, MDCT and pulmonary function test. Mean relative enhancement ratio on O₂-enhanced MRI and CT-base functional lung volume on quantitative CT were computationally calculated. To compare the efficacy of O₂-enhanced MRI and quantitative CT for pulmonary functional loss assessment, both indexes were correlated with pulmonary functional parameters. To determine the efficacy of two methods for clinical stage classification, the four clinical groups' mean relative enhancement ratio and CT-based functional lung volume were statistically compared. Measurements and Main Results: Correlations of both indexes with pulmonary functional parameters were significant (p<0.0001). Pulmonary functional parameters and mean relative enhancement ratio for the four clinical groups showed significant differences (p<0.05). CT-based functional lung volumes of 'Smokers without COPD' and 'Mild COPD' were significantly different from those for 'Moderate COPD' and 'Severe or Very Severe COPD' (p<0.05). Conclusions: O₂-enhanced MRI is effective for pulmonary functional loss assessment and clinical stage classification of smoking-related COPD as well as quantitative CT.