STUDY OBJECTIVES To assess the potential benefit of thrombolysis in patients with massive pulmonary embolism (PE) with stable hemodynamics and right ventricular dysfunction. DESIGN Retrospective, cohort study. SETTING University-based, tertiary referral medical center. PATIENTS One hundred fifty-three consecutive patients with massive PE from January 1992 to December 1997 treated with heparin or thrombolysis. MEASUREMENTS AND RESULTS Massive PE was confirmed by perfusion lung scan or pulmonary angiography. Right ventricular dysfunction was assessed by echocardiography (right ventricular/left ventricular [RV/LV] diastolic diameter ratio > 0.6) in all patients. In order to study a homogeneous population, 64 patients treated with thrombolysis (group 1) were matched on baseline RV/LV diameter ratio to 64 patients treated with heparin (group 2). Perfusion lung scan was repeated at day 7 to day 10. Mean relative improvement in perfusion lung scans was higher in group 1 than group 2 (54% vs 42%, respectively). PE recurrences were the same in both groups (4.7%; n = 3). There were no bleeding complications and no deaths in group 2. Conversely, in group 1, 15.6% (n = 10) of patients suffered from bleeding (4.7%; n = 3 with intracranial bleeding) and 6.25% (n = 4) of them died. CONCLUSIONS The results of this monocenter registry do not support the indication for thrombolysis in patients suffering from massive PE with stable hemodynamics and right ventricular dysfunction. Appropriate therapy in such patients still remains unknown. Further prospective randomized trials should be performed.