Invasive hemodynamic assessment remains the gold standard for the diagnosis of pediatric pulmonary hypertension and for longitudinal assessment of response to therapy. This analysis sought to describe the changes in hemodynamic variables after initiation of prostacyclin therapy and determine which changes bear predictive power of adverse clinical outcomes. A retrospective chart review of established patients at Cincinnati Children’s Hospital with pulmonary arterial hypertension (PAH) who required prostacyclin therapy between 2004 and 2018 was performed. The baseline hemodynamic parameters at diagnosis as well as change in those parameters between initial catheterization and post-prostacyclin initiation catheterization were independent variables. Cox proportional hazard regression and recursive partitioning analysis were used to characterize which hemodynamic factors predicted the composite adverse outcome (CAO) defined as death, lung transplantation, or reverse Pott’s shunt surgery. During the study period, 29 patients met inclusion criteria in which there were 7 CAOs: 4 deaths, 3 lung transplants, and 2 reverse Pott’s shunts. Median time between catheterizations was 86 days and between the initiation of prostacyclin therapy and the second catheterization was 54 days. Cox regression revealed that only baseline pulmonary artery pressure (> 51 mmHg) and a failure to increase cardiac index illustrated statistically significant hazard for occurrence of the CAO (p < 0.01). These criteria significantly dichotomized the population in a Kaplan–Meier analysis into likelihoods of experiencing the CAO. While controlling for other hemodynamic variables, the absence of augmentation of cardiac index after the initiation of prostacyclin therapy is a valuable prognostic indicator of adverse PAH outcomes in pediatrics.