Background: In Japan, the safety and efficacy of thrombolytic therapy using tissue-type plasminogen activator for acute pulmonary embolism (PE) in the real world remain unclear. Methods and Results: A total of 1,254 patients with acute PE covered by the post-marketing surveillance of thrombolytic therapy using monteplase were divided into 3 groups: cardiopulmonary arrest (CPA)/collapse group (n=85); massive group, patients with unstable hemodynamics without CPA/collapse (n=217); and submassive group, patients with stable hemodynamics and right ventricular dysfunction (RVD) (n=465). In the efficacy analysis of 767 cases, the response rate to monteplase was 94.6% according to pulmonary circulation assessment and 93.3% according to clinical efficacy judged by symptoms and signs. Overall survival rates at 30 days after monteplase administration were 89.2% overall, 41.2% for the CPA/collapse group, 93.0% for the massive group, and 96.3% for the submassive group. When the safety of monteplase was analyzed in 1,241 cases, severe bleeding complications occurred in 100 patients (8.1%). Intracranial hemorrhage (ICH) occurred in 21 patients (1.7%), but no significant independent predictors were found in multivariate analysis. Conclusions: Thrombolytic therapy is highly effective in Japanese acute PE patients and offers acceptable safety, but attention is needed regarding severe bleeding complications, including ICH.  (Circ J 2012; 76: 2471–2480)