Data from the TOPP-2 registry showed wide variation in initial treatment strategies for pediatric pulmonary arterial hypertension (PAH). Patients whose therapy was escalated during the first year—from single to dual therapy in lower-risk patients or to TripleX therapy in higher-risk patients—had worse outcomes than those who received more intensive combination therapy from the outset. Pediatric pulmonary arterial hypertension (PAH) carries high mortality with 81% 5-year transplant-free survival. The global Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension-2 (TOPP-2; NCT02610660) registry was created to assess the treatments and outcomes of newly diagnosed pediatric PAH patients. Keywords:Upfront, Combination, Therapy, Improve, Outcomes, Pediatric, PAH, Study, Frank, Benjamin S