Background: To evaluate the safety and efficacy of selective catheter-directed thrombolysis (SCDT) in treating acute massive pulmonary thromboembolism (AMPTE). Methods: Twenty-six AMPTE patients were enrolled between March 2010 and March 2013. A Uni*Fuse infusion system was inserted into the main pulmonary artery thrombus. The thrombolytic regimen included an intraoperative bolus injection of 250,000 IU urokinase, followed by continuous thrombolytic infusion of 5,000 IU/kg per (every) 24 hr urokinase for 72 hr postoperatively. Clinical symptoms, shock index (SI), systolic pulmonary artery pressure (sPAP), peripheral arterial partial pressure of oxygen (PaO2), and Miller index (MI) were assessed before and after treatment. Results: The patients included 16 men and 10 women (49.9 +/- 18.8 years old; time to onset of 50.2 +/- 28.5 hr). After thrombolysis, dyspnea and cough were relieved to varying degrees; chest pain, hemoptysis, and syncope disappeared. Importantly, a clinical success rate of 100% was achieved. All objective indices were improved: SI decreased from 1.74 +/- 0.38 before operation to 0.71 +/- 0.09 postoperatively (P = 0.00); PaO2 increased from 52.78 +/- 6.92 mm Hg to 85.98 +/- 5.91 mm Hg (P = 0.00); sPAP was reduced from 65.19 +/- 8.22 mm Hg to 34.42 +/- 4.05 mm Hg (P = 0.00); MI dropped from 0.69 +/- 0.09 to 0.33 +/- 0.06 (P = 0.00). Mean total urokinase amounts were 1,298,000 IU for each patient. Postoperative complications included 2 cases of puncture-site hematoma (cured by pressure bandage) and 1 case of gastrointestinal hemorrhage (healed by conservative treatment without blood transfusion). Conclusions: SCDT may be considered a safe and efficacious treatment for AMPTE.