AimExtracorporeal membrane oxygenation (ECMO) may be beneficial in treatment of massive pulmonary embolus (PE), however the current evidence to guide its use is limited. We aimed to compare the incidence, characteristics, treatments, and outcomes of patients with massive PE by mode of ECMO from a large international registry. MethodsRetrospective observational study of the Extracorporeal Life Support Organization (ELSO) database. ResultsA total of 821 patients underwent 833 ECMO episodes for PE. Mean age was 49 (±15) years, 408 (50.1%) were female, and 450 (54.7%) had a cardiac arrest prior to ECMO initiation. Venoarterial (VA) ECMO was the most common mode in 489 (58.7%), followed by extracorporeal cardiopulmonary resuscitation (ECPR) in 229 (27.4%) and venovenous (VV) ECMO in 85 (10.2%). The number of episodes per year increased over the study period, predominantly driven by an increase in ECPR. In-hospital mortality was the highest for ECPR 156/229 (68.1%), followed by VA ECMO 209/498 (42.7%) and VV ECMO 24/85 (28.2%) P < 0.001. After controlling for univariate and clinically significant variables at the time of ECMO initiation, increasing age (OR 1.02 (1.00–1.03), lower pH (OR 0.18 (0.03–0.44), lower diastolic blood pressure (OR 0.99 (0.97–1.00) and ECPR mode (OR 3.67 (1.46–9.230) were independently associated with in-hospital mortality. ConclusionECMO use for massive PE is increasing globally, and overall mortality rates compare favorably with other indications of ECMO. The use of ECPR and worsening metabolic status at initiation were associated with higher in-hospital mortality, suggesting delays in initiating ECMO should be avoided.