Rationale and Objectives: Pulmonary vascular alteration is one of the characteristic features of chronic obstructive pulmonary disease (COPD). Recent studies suggest that vascular alteration is closely related to endothelial dysfunction and may be further influenced by emphysema. However, the relationship between morphological alteration of small pulmonary vessels and the extent of emphysema has not been assessed in vivo. The objectives of this study are: to evaluate the correlation of total cross-sectional area (CSA) of small pulmonary vessels with the extent of emphysema and airflow obstruction using CT scans and to assess the difference of total CSA between COPD phenotypes. Materials and Methods: We measured CSA less than 5 mm2 and 5-10 mm2, and calculated the percentage of the total CSA for the lung area (%CSA < 5, and %CSA5-10, respectively) using CT scans in 191 subjects. The extent of emphysema (%LAA-950) was calculated, and the correlations of %CSA < 5 and %CSA5-10 with %LAA-950 and results of pulmonary function tests (PFTs) were evaluated. The differences in %CSA between COPD phenotypes were also assessed. Results: The %CSA < 5 had significant negative correlations with %LAA-950 (r = -0.83, P < .0001). There was a weak but statistically significant correlation of %CSA < 5 with forced expiratory volume in 1 second (FEV1)% predicted (r = 0.29, P < .0001) and FEV1/forced vital capacity (r = 0.45, P < .0001). A %CSA 5-10 had weak correlations with %LAA-950 and results of PFTs. %CSA < 5 was significantly higher in bronchitis phenotype than in the emphysema phenotype (P < .0001). Conclusions: Total CSA of small pulmonary vessels at sub-subsegmental levels strongly correlates with the extent of emphysema (%LAA-950) and reflects differences between COPD phenotypes. © 2010 AUR.