Extracorporeal cardiopulmonary resuscitation (ECPR) is an emerging rescue strategy for select patients with refractory out-of-hospital cardiac arrest (OHCA). Mobile ECPR programs aim to reduce low-flow time by initiating extracorporeal membrane oxygenation (ECMO) before hospital arrival. Here we report the first ECPR performed within a patient’s home in North America. We describe a 66-year-old woman with witnessed ventricular fibrillation OHCA who underwent successful venoarterial ECMO cannulation on scene, on the floor of her bedroom by a mobile ECMO team. Cannulation was performed under challenging conditions, including confined residential space, ongoing mechanical cardiopulmonary resuscitation, limited lighting, and improvised equipment placement. Following ECMO initiation, the patient converted to sinus rhythm, was transported directly to the cardiac catheterization laboratory, and achieved recovery of left ventricular systolic function before discharge. This case demonstrates the feasibility of on-scene, residential ECPR cannulation within a large metropolitan environment and highlights the critical importance of operational logistics, team coordination, and environmental adaptability. As mobile ECPR programs expand, systems-level considerations may be as important as technical cannulation expertise.