The purpose of this study was to determine the efficacy of inhaled epoprostenol for treatment of acute pulmonary hypertension (PH) in pediatric patients and to formulate a plan for a prospective, randomized study of pulmonary vasodilator therapy in this population. Inhaled epoprostenol is an effective treatment for pediatric PH. A retrospective chart review was conducted of all pediatric patients who received inhaled epoprostenol at a tertiary care hospital between October 2005 and August 2007. The study population was restricted to all patients under 18 years of age who received inhaled epoprostenol for greater than 1 hour and had available data for oxygenation index (OI) calculation. Arterial blood gas values and ventilator settings were collected immediately prior to epoprostenol initiation, and during epoprostenol therapy (as close to 12 hours after initiation as possible). Echocardiograms were reviewed during two time frames: Within 48 hours prior to therapy initiation and within 96 hours after initiation. Of the 20 patients in the study population, 13 were neonates, and the mean OI for these patients improved during epoprostenol administration (mean OI before and during therapy was 25.6±16.3 and 14.5±13.6, respectively, P=0.02). Mean OI for the seven patients greater than 30 days of age was not significantly different during treatment (mean OI before and during therapy was 29.6±15.0 and 25.6±17.8, P=0.56). Improvement in echocardiographic findings (evidence of decreased right-sided pressures or improved right ventricular function) was demonstrated in 20% of all patients. Inhaled epoprostenol is an effective therapy for the treatment of selected pediatric patients with acute PH. Neonates may benefit more consistently from this therapy than older infants and children. A randomized controlled trial is needed to discern the optimal role for inhaled prostanoids in the treatment of acute PH in childhood.