Intravascular and intracardiac masses are usually represented by thrombi, tumours, and vegetations. They can affect both the right and left chambers of the heart and the venous and arterial circulation. Traditionally, their treatment is surgical or, in some circumstances, based on systemic anticoagulation/fibrinolysis. However, the complexity and frailty of patients who sometimes present with these conditions have pushed surgeons to find alternative minimally invasive effective treatments. While small masses can be removed with multiple devices, large masses are a more challenging problem. Vacuum-assisted aspiration systems such as the AngioVac System were developed to treat intravenous and right-sided heart thrombi. The application of the AngioVac System was widened to right-sided endocarditis and, later, to left-sided thrombi and vegetations. This review summarises the clinical results of different uses of the vacuum-assisted aspiration system to treat intravenous and intracardiac masses.