Introduction: Pulmonary arterial hypertension (PAH) is a common and fatal complication of congenital heart disease (CHD). PAH-CHD increases the risk for postoperative complications. Recent evidence suggests that perioperative goal-directed hemodynamic optimization therapy (GDHOT) significantly improves outcomes in surgery patients. Standard GDHOT is based on major solution volume, vasodilators and inotropic therapy, while novel GDHOT is based on major vasopressor and inotropic therapy. Therefore, we tested whether standard or novel GDHOT improves surgical outcomes in PAH-CHD patients. Methods: Forty PAH-CHD patients with a ventricular septal defect (VSD) and mean pulmonary arterial pressure (mPAP) >50 mmHg, who were scheduled for corrective surgery, were randomly assigned to 2 groups: SG (study group, n = 20) and CG (control group, n = 20). SG patients received perioperative hemodynamic therapy guided by novel GDHOT, while CG patients received standard GDHOT. Outcome data were recorded up to 28 days postoperatively. Ventilator time, length of ICU stay, and mortality were the primary endpoints. Results: There were no significant differences in preoperative data, surgical procedure, and hospital mortality rates between the 2 groups. Time of mechanical ventilation and length of ICU stay were significantly shorter in SG patients compared to CG patients (P <.05, n = 20). Patients in SG showed a significantly increased systemic vascular resistance index and decreased cardiac index, but no change in pulmonary vascular resistance index at 12 and 24 hours after surgery compared to the controls (P < .05). Patients in SG had significantly decreased PAP, pulmonary arterial pressure/systemic arterial pressure (Pp/Ps), and RVSWI (right ventricular stroke work index) at 12 and 24 hours after surgery (P < .05, respectively). Patients in SG also showed significantly decreased central venous pressure at 4, 12, and 24 hours after surgery compared to those treated with standard protocol (P < .05). Conclusion: Our study provides clinical evidence that perioperative goal-directed hemodynamic optimization therapy based on major vasopressor is associated with reduced duration of postoperative respiratory support, and length of ICU stay in PAH-CHD patients undergoing elective surgery. These outcomes, then, may be linked to improved hemodynamics and preservation of right ventricular dynamic function.