Essentials The evidence on how to manage life-threatening pregnancy-related pulmonary embolism (PE) is scarce. We systematically reviewed all available cases of (sub)massive PE until December 2016. Thrombolysis in such severe PE was associated with a high maternal survival (94%). The major bleeding risk was much greater in the postpartum (58%) than antepartum period (18%). SUMMARY:Background Massive pulmonary embolism (PE) during pregnancy or the postpartum period is a rare but dramatic event. Our aim was to systematically review the evidence to guide its management. Methods We searched Pubmed, Embase, conference proceedings and the RIETE registry for published cases of severe (submassive/massive) PE treated with thrombolysis, percutaneous or surgical thrombectomy and/or extracorporeal membrane oxygenation (ECMO), occurring during pregnancy or within 6 weeks of delivery. Main outcomes were maternal survival and major bleeding, premature delivery, and fetal survival and bleeding. Results We found 127 cases of severe PE (at least 83% massive; 23% with cardiac arrest) treated with at least one modality. Among 83 women with thrombolysis, survival was 94% (95% CI, 86-98). The risk of major bleeding was 17.5% during pregnancy and 58.3% in the postpartum period, mainly because of severe postpartum hemorrhages. Fetal deaths possibly related to PE or its treatment occurred in 12.0% of cases treated during pregnancy. Among 36 women with surgical thrombectomy, maternal survival and risk of major bleeding were 86.1% (95% CI, 71-95) and 20.0%, with fetal deaths possibly related to surgery in 20.0%. About half of severe postpartum PEs occurred within 24 h of delivery. Conclusions Published cases of thrombolysis for massive PE during pregnancy and the postpartum period suggest a high maternal and fetal survival (94% and 88%). In the postpartum period, given the high risk of major bleeding with thrombolysis, other therapeutic options (catheter [or surgical] thrombectomy, ECMO) may be considered if available.