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The treatment of choice for congenital heart disease (CHD) with pulmonary arterial hypertension (PAH) is still controversial. We assessed the efficacy and safety of perioperative inhaled iloprost therapy in CHD with PAH.Among 45 patients with a ventricular septal defect and/or an atrial septal defect with PAH, 28 patients were treated with inhaled iloprost before and after surgery. Perioperative clinical parameters and plasma B-type natriuretic peptide (BNP) were evaluated.No statistical difference in the estimated right ventricular systolic pressure (e-RVP), the e-RVP-to-systemic pressure ratio, and preoperative BNP levels between the iloprost group and the control group were found. Among the iloprost group, oxygen saturation was increased significantly after iloprost inhalation therapy (p = 0.0052). The iloprost group was also significantly correlated with less use of inhaled nitric oxide in the immediate postoperative period compared to the control group (p = 0.021). The durations of mechanical ventilation (p = 0.018), ICU stay (p = 0.005), and chest tube use (p = 0.039) were significantly shorter in the iloprost group compared to the control group. The plasma BNP, checked on 7th day of postoperatively, was lower in the iloprost group than in the control group (p = 0.008).Perioperative inhaled iloprost therapy showed the benefit of cardiac functional improvement and early weaning of postoperative supportive care in the management of CHD with PAH.