BACKGROUND Systemic thrombolysis with tissue plasminogen activator (t-PA) in pregnancy is still considered an experimental treatment. Several reports have described the successful use of t-PA in the setting of hemodynamic instability in gravidas with massive pulmonary emboli. METHODS A 34-year-old woman received a diagnosis of severe pulmonary embolism at 23 weeks of gestation. She developed pulmonary hypertension and became hemodynamically unstable. Thrombolytic therapy using t-PA was administered. The patient tolerated thrombolysis well and delivered at term. No placental abnormalities were identified on ultrasonogram or after delivery. The patient was also found to be a heterozygous carrier of prothrombin G20210A mutation. CONCLUSIONS We describe the successful thrombolysis with t-PA of a massive, life-threatening pulmonary embolism without complications followed by a term delivery.