Objective To determine normal four-extremity blood pressure (BP) in the NICU at birth and the utility of upper (UE) and lower extremity (LE) BP difference to screen for coarctation of aorta (Co-A) and interrupted aortic arch (IAA). Study Design Retrospective study of BP at birth (n=866), and case-control study of Co-A/IAA infants and matched controls (1:2). Results Although BP increased with gestational age (R2=0.3, p<0.0001), the pressure gradient between UE and LE did not change with gestation (p=0.68). Forty-six cases of Co-A/IAA were identified, with 92 controls. Pressure gradient was significantly higher in patients with Co-A/IAA (7.6±14.8 vs.0.4±10mmHg, p=0.004). However, there was overlap between cases and controls resulting in low sensitivity (41.3% with ≥10mmHg gradient cut-off). Conclusion Evaluation of UE-LE BP gradient at birth is a poor screening test for Co-A/IAA with low sensitivity. Repeating four-limb BP after ductal closure at 24–48h along with SpO2 screening for critical congenital heart disease may increase sensitivity.