Respiratory distress syndrome (RDS) secondary to surfactant deficiency is a common cause of morbidity and mortality in premature infants. An increasing evidence suggests that vascular endothelial growth factor (VEGF) may contribute to surfactant secretion and pulmonary maturation. This study determines cord blood VEGF levels in preterm infants and investigates its association with the development and severity of RDS. 50 preterm neonates and 10 healthy full term neonates were included in this study. All preterm neonates were subjected to full history taking, complete clinical examination, chest X-ray and laboratory investigations including arterial blood gases, CBC and C-reactive protein. Cord blood samples were obtained for determination of VEGF levels using ELISA. Cord blood VEGF level was significantly lower in preterm infants with RDS (7.76 +/- 2.28 in mild cases and 3.64 +/- 1.22 in severe cases) as compared to preterm infants without RDS (16.61 +/- 4.58) and controls (16.48 +/- 3.23) (p < 0.001). Infants with severe RDS especially those with small gestational age (GA), low birth weight (BW) and low APGAR score at 1 and 5 minutes had significantly lower cord blood VEGF level than those with mild RDS (p < 0.001). There was no significant effect on the level of VEGF regarding maternal use of antenatal steroids, premature rupture of membrane (PROM) and sex of newborn infants (P > 0.05). The sensitivity and specificity of cord blood VEGF test was 80% and 62% respectively with positive predictive value (PPV) of 80% and negative predictive value 56% at cutoff point of 10.02 ng/mL. It's concluded that cord blood VEGF elevation is associated with the absence of RDS, and that its level negatively correlates with the severity of the disease and duration on ventilation.