Rationale: The pathogenesis of chronic obstructive pulmonary disease is not fully understood. Objectives: To compare circulating endothelial progenitor cells in patients with chronic obstructive pulmonary disease to age, gender and cigarette smoking matched healthy controls. Methods and Measurements: Patients with chronic obstructive pulmonary disease (n=37) and healthy controls (n=19) were matched by age, gender and smoking status. Circulating hematopoietic progenitor cells (CD34+ or CD133+ mononuclear cells) and endothelial progenitor cells (CD34⁺KDR⁺ or CD34⁺CD133⁺KDR⁺ mononuclear cells) were quantified by flow cytometry. Endothelial cell-colony forming units from peripheral blood mononuclear cells were quantified in vitro and phenotypic analysis carried out using immunocytochemistry. Main Results: Patients with chronic obstructive pulmonary disease had more circulating mononuclear cells compared to controls (8.4±0.6 versus 5.9±0.4 x109 cells/L; P=0.02). CD34⁺ hematopoietic progenitor cells were reduced as a proportion of mononuclear cells in patients compared to controls (0.99±0.12 versus 1.9±0.12%; P=0.02), however there were no differences in the absolute number of CD34+, CD34⁺KDR⁺ or CD34⁺CD133⁺KDR⁺ cells (P>0.05 for all). Endothelial cell-colony forming units were increased in patients with chronic obstructive pulmonary disease compared to controls (13.7±5.2 versus 2.7±0.9 colonies; P=0.048). Conclusions: In contrast to previous studies the number of circulating progenitor cells were not reduced in patients with chronic obstructive pulmonary disease compared with carefully matched controls. It seems unlikely that circulating endothelial progenitor cells or failure of angiogenesis play a central role in the development of emphysema.