Inhaled prostacyclin analogue iloprost is currently utilized in adult patients with pulmonary arterial hypertension (PAH), but little information is available on its use in the pediatric population. This study evaluated the safety and acute haemodynamic effects of inhaled iloprost in children with PAH associated with congenital heart disease (CHD). Children with PAH-CHD who underwent cardiac catheterization and iloprost administration in our catheter laboratory between June 2007 and October 2015 were included. Iloprost was administered by atomization inhalation and changes in hemodynamic parameters were recorded. In total, 100 children with PAH-CHD were enrolled. Median age was 13 [1.5-18.0] years and 34% were male. A ventricular septal defect was present in 84%, a patent duct in 12%, a complete atrioventricular septal defect in 2%, and an isolated atrial septal defect in 2%. Pulmonary vascular resistance indexed (PVRI) was above 8 WU m(2) in 96% and was above a third systemic (R (p)/R (s) > 0.33) in 97%. Iloprost was well tolerated in all patients. Following iloprost inhalation, mean pulmonary arterial pressure decreased from 78.4 +/- 9.2 to 72.8 +/- 10.8 mmHg (p < 0.01) and pulmonary-to-systemic blood flow ratio (Q (p)/Q (s)) increased from 1.12 +/- 0.48 to 1.37 +/- 0.63 (p < 0.01), with no change in cardiac index (Q (s)). PVRI decreased from 21.0 +/- 9.0 to 16.9 +/- 8.0 WU m(2) (p < 0.01) following inhalation but 92% patients still had a PVRI > 8 WU m(2) and 93% an R (p)/R (s) > 0.33. Acute inhalation of iloprost in children with PAH associated with CHD resulted in a significant improvement in hemodynamic parameters. Despite this, few patients achieve strict criteria of operability, underscoring the importance of early screening and timely repair of CHD.