Rationale: Preterm birth and hyperoxic exposure increase the risk for bronchopulmonary dysplasia (BPD), a chronic lung disease characterized by impaired vascular and alveolar growth. Endothelial progenitor cells, such as self-renewing highly-proliferative endothelial colony-forming cells (ECFCs), may participate in vascular repair. The effect of hyperoxia on ECFC growth is unknown. Objectives: We hypothesize that umbilical cord blood (CB) from premature infants contains more ECFCs with greater growth potential than term CB. However, preterm ECFCs may be more susceptible to hyperoxia. Methods: ECFC colonies were quantified by established methods and characterized by immunohistochemistry and flow cytometry. Growth kinetics were assessed in room air and hyperoxia (FiO2=0.4). Measurements and Main Results: Preterm CB (28-35 weeks gestation) yielded significantly more ECFC colonies than term CB. Importantly, we found that CD45-/CD34+/CD133+/VEGFR-2+ cell number did not correlate with ECFC colony count. Preterm ECFCs demonstrated increased growth as compared to term ECFCs. Hyperoxia impaired growth of preterm but not term ECFCs. Treatment with superoxide dismutase and catalase enhanced preterm ECFC growth during hyperoxia. Conclusions: Preterm ECFCs appear in increased number and proliferate more rapidly, but have an increased susceptibility to hyperoxia as compared to term ECFCs. Antioxidants protect preterm ECFCs from hyperoxia.