Post-infarct ventricular septal defect (PIVSD) is a rare, life-threatening complication following acute myocardial infarction (MI), associated with high overall mortality. Interventions include medical management, percutaneous closure, and/or surgical closure. Of these, delayed surgical closure is associated with the highest survivorship at 30 days and 1 year, necessitating early medical stabilization for an optimal surgical outcome. Consequently, patients with PIVSD often require mechanical circulatory support (MCS), namely intra-aortic balloon pump (IABP) and/or veno-arterial extra-corporeal membrane oxygenation (VA ECMO) and are likely faced with prolonged preoperative phases with associated immobility. Available case reports document length of stays between 19 days to 8 weeks, associated with complications related to immobilization. There is a dearth of evidence that supports the mobilization of patients with PIVSD while supported on MCS. Accordingly, we present a novel case of a critically ill 61-year-old male with a 2.72 cm PIVSD, supported with femoral IABP and femoral VA ECMO, that safely and successfully participated in physical therapy (PT), including ambulation (mean 109 ft.) during 10 sessions over 18 days while awaiting surgical repair. In addition, we discuss the use of transthoracic echocardiography (TTE) at rest and during exercise demonstrating improvement in all measures of RV systolic function (RVOT VTI, RV Free Wall S’, TAPSE) as well as a reduction in shunt ratio (Qp:Qs) with exertion. This experience detailing early PT intervention/ambulation with TTE measures of RV function provides one model for the safe management of patients with PIVSD supported on MCS devices awaiting surgical intervention.