Extracorporeal membrane oxygenation (ECMO) utilization for primary pulmonary hypertension (PPHTN) remains controversial. This multicenter, retrospective analysis of the Extracorporeal Life Support Organization Registry evaluated 221 PPHTN patients placed on ECMO in 2000-2019. Survival by ECMO indications and cannulation strategies were compared with Kaplan-Meier analyses. ECMO mortality risk factors were analyzed using Cox proportional hazards regressions. The overall rate of survival to ECMO decannulation was 140/221 (63.3%), of which 112/140 (80.0%) survived to hospital discharge. Survival to decannulation increased between 2000-2009 (14/30, 46.7%) and 2010-2019 (126/191, 66.0%, p = 0.041) alongside survival to hospital discharge (9/30, 30.0% vs. 103/191, 53.9%, p = 0.015). Survival to decannulation was similar when patients were supported with either venovenous-ECMO (VV-ECMO
39/54, 72.2%) or venoarterial-ECMO (VA-ECMO) for respiratory failure (43/71, 60.6%, p = 0.174), although VV-ECMO was associated with fewer complications (25/54, 46% vs. 25/71, 35%, respectively, p = 0.039) and increased survival to hospital discharge (34/54, 63.0% vs. 33/71, 46.5%, p = 0.067). The strongest independent predictor of ECMO morality was isolated vasopressor use before cannulation (hazard ratio [HR]: 3.37 [95% confidence interval {CI95%}: 1.16-9.81], p = 0.026). Extracorporeal membrane oxygenation mortality risk was lower among patients bridged-to-transplantation (HR: 0.37 [CI95%: 0.14-0.97], p = 0.043), and was inversely correlated with pre-ECMO pH (HR: 0.03 [CI95%: 0.00-0.49], p = 0.013). Extracorporeal membrane oxygenation use for PPHTN has grown alongside improved outcomes. Early ECMO initiation may improve outcomes in select individuals with PPHTN.