Rationale: Angiographic investigation suggests that pulmonary vascular remodeling in smokers is characterized by distal pruning of the blood vessels. Objectives: Using volumetric computed tomography scans of the chest we sought to quantitatively evaluate this process and assess its clinical associations. Methods: Pulmonary vessels were automatically identified, segmented, and measured. Total blood vessel volume (TBV) and the aggregate vessel volume for vessels less than 5 mm2 (BV5) were calculated for all lobes. The lobe-specific BV5measures were normalized to the TBV of that lobe and the nonvascular tissue volume (BV5/ TissueV) to calculate lobe-specific BV5/TBV and BV5/TissueV ratios. Densitometric measures of emphysema were obtained using a Hounsfield unit threshold of2950 (%LAA-950).Measures of chronic obstructive pulmonary disease severity included single breath measures of diffusing capacity of carbon monoxide, oxygen saturation, the 6-minute-walk distance, St George's Respiratory Questionnaire total score (SGRQ), and the body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index. Measurements and Main Results: The %LAA-950 was inversely related to all calculated vascular ratios. In multivariate modelsincluding age, sex, and%LAA-950, lobe-specificmeasurements of BV5/TBVwere directly related to resting oxygen saturation and inversely associated with both the SGRQ and BODE scores. In similar multivariate adjustment lobe-specific BV5/TissueV ratios were inversely related to resting oxygen saturation, diffusing capacity of carbon monoxide, 6-minutewalk distance, and directly related to the SGRQ and BODE. Conclusions: Smoking-related chronic obstructive pulmonary disease is characterized by distal pruning of the small blood vessels (,5mm2) and loss of tissue in excess of the vasculature. Themagnitude of these changes predicts the clinical severity of disease. Copyright © 2013 by the American Thoracic Society.