Background: Pulmonary hypertension of the neonates (PHN) is a syndrome that is distinguished by severe hypoxemia, right-to-left shunt, & elevated pulmonary vascular resistance, all of which are absent indicators of congenital heart disorders. Objective: This research aimed to compare between either of Sildenafil or magnesium sulfate alone versus combination of both as treatment for pulmonary hypertension in newborns. Patients and methods: This prospective case-control research was performed on 100 patients (newborns) who had pulmonary hypertension. They were admitted to Neonatal Intensive Care Unit (NICU) at EL Kharga specialized hospital at El Wadi El Gadid. Our cases were separated into three groups: Group A included 30 newborns who were treated with sildenafil, group B contained 30 newborns who were treated with magnesium sulfate and group C that comprised 40 newborns who were treated with both sildenafil plus magnesium sulfate. Results: There wasn't significant variance among the studied groups regarding echo parameters in all parameters (P > 0.05). There wasa significant decrease regarding expiratory positive airway pressure (EPAP) in all groups. However, the reduction was better among group C compared to groups A & B (P < 0.001).Hypotension incidence was significantly lower among group C compared to the other groups (P=0.024). Conclusion: Magnesium sulfate and sildenafil are safe pulmonary vasodilators for persistent pulmonary hypertension (PPHN) treatment, serving as rescue therapy. Combining these drugs improved the recovery of newborns with PPHN, surpassing monotherapy with only MgSO₄ or sildenafil.