Background: In bronchopulmonary dysplasia (BPD), disrupted angiogenesis may result from an imbalance between pro- and anti-angiogenic factors triggered by inflammation and lead to the late development of pulmonary artery hypertension ( PAH). Objectives: To investigate whether levels of serum endostatin (as an anti-angiogenic factor) and angiopoietin-1 (as a pro-angiogenic factor) in early life are associated with the development of PAH in preterm infants with severe BPD. Methods: In this prospective cohort study, a total of 56 infants (gestational age 30 weeks or a birth weight 1,250 g) including severe BPD with PAH (‘PAH’; 15 infants) or without PAH (‘non-PAH’; 22 infants) and no/mild BPD (19 infants) groups underwent endostatin and angiopoietin-1 in serum determinations on days 1, 7, 14, and 28 of life. Results: The serum endostatin levels were not significantly different between the severe and no/mild BPD groups on days 1, 7, 14, and 28 of life. However, the serum endostatin level on day 7 was higher in the PAH group than in the non-PAH or no/mild BPD groups (median 146.6 vs. 102.4 ng/ml, p = 0.000; 146.6 vs. 108.0 ng/ml, p = 0.003). The serum endostatin levels on days 1, 14, and 28 and the serum angiopoietin-1 levels on days 1, 7, 14, and 28 were not significantly different among the three groups. The serum endostatin to angiopoietin-1 ratio on day 7 was also higher in the PAH group than in the non-PAH or no/mild BPD groups (median 62.1 vs. 18.6, p = 0.000 ; 62.1 vs. 14.9, p = 0.034). Conclusions: The increased serum endostatin to angiopietin-1 ratio may reflect impaired angiogenesis that may prelude the development of PAH.