Despite many advances in the identification of cardiac and vascular thrombi, research of critical components within thrombotic structures, understanding the impact of thrombotic mass on clinical outcome, and availability of various extraction and removal technologies, the optimal choice of treatment for large intracardiac or caval thrombi remains an enigma. Frequently, these patients present in markedly unstable hemodynamic condition; thus, the discovery of intracardiac or venous vasculature thrombi constitutes an ominous harbinger of clinical complications calling for urgent treatment. Left untreated, especially in patients with infected thrombotic mass, the mortality can be exceptionally high. In these clinical scenarios, patients who carry a large thrombus in transit with concurrent pulmonary embolism constitute a unique management group. At the same time, those without evidence of pulmonary embolism (yet …) who exhibit vena cava, subclavian, right cardiac thrombotic mass, vegetation, or tumor constitute a no-less-challenging group. Their risk of distal embolization and subsequent major pulmonary insult is profound.