Acute major pulmonary artery embolism (AMPE) requires rapid diagnosis and early intensive treatment to optimize patient outcomes. Most patients with AMPE and hemodynamic instability need open pulmonary embolectomy (OPE). We modified the technique of OPE to include a minimally invasive procedure without the use of cardiopulmonary bypass (CPB). From March 1988 to April 2006, we performed OPE on a total of 12 patients (21 sides) with AMPE. Seven patients (13 sides) underwent conventional OPE with CPB and 5 patients underwent off-pump OPE (OPPE), 4 (8 sides) with AMPE and 1 with catheter embolus with thrombosis. In patients who underwent conventional OPE, there was 1 hospital death in a patient with severe right ventricle dysfunction and 2 significant cases of airway bleeding. In patients who underwent OPPE, there was 1 case of minimal airway bleeding. Mean systolic pulmonary artery pressure in conventional OPE and OPPE patients, respectively, decreased from 50.3 +/- 14 mmHg and 35.4 +/- 6.6 mmHg pre-operatively to 41.7 +/- 20 and 28 +/- 3 mmHg postoperatively. During the long-term follow-up, there were 2 cancer-related deaths but no recurrence of PE. All surviving patients maintained functional class I (n = 10) or II (n = 1). Compared with conventional OPE, OPPE was effective for treating AMPE in our selected cases. Modification of conventional CPB and systemic full heparinization to minimal use of systemic heparinization without CPB may be helpful in treating selected patients with AMPE.