Objective: Among neonates undergoing whole body cooling for hypoxic-ischemic encephalopathy (HIE), to compare ventricular function in the presence and absence of pulmonary hypertension (PPHN) needing inhaled nitric oxide (iNO)/ECMO. Design: This retrospective study included infants with HIE who underwent cooling. ECHO (<24 h age) measures, RV fractional area change (FAC), RV Tricuspid annular plane systolic excursion (TAPSE), myocardial performance indices (MPI), and the RV systolic to diastolic duration (S/D) ratio were evaluated. Results: The iNO/ECMO group (n = 26) had lower TAPSE and RV FAC and higher RV MPI and S/D, compared with controls (n = 39). Area under the curve was highest for RV S/D, with fair sensitivity (95% CI) [76.9 (56.3–91%)] and negative predictive value [78.6 (63.3–88.6%)] for subsequent iNO/ECMO at cutoff >1.45. Conclusions: Infants with HIE undergoing cooling who progressed to iNO/ECMO for PPHN had RV dysfunction on early ECHO; S/D had the best predictive performance. RV S/D may be a useful early marker of PPHN in HIE.