Lumivascular optical coherence tomography (OCT) is a novel adjunct in the field of medicine. It offers clear real-time imaging of artery walls before and during endovascular intervention. This study reports our initial experience on the use of lumivascular OCT-guided atherectomy in the management of two patients with recurrent restenosis in their femoropopliteal arteries associated with in-stent restenosis. Endovascular procedures were successful with a Pantheris atherectomy device (Avinger, Redwood City, CA, USA) and drug-eluting balloons. The OCT images clearly distinguished normal anatomy from plaque pathology, were of great advantage in both the accurate diagnosis and treatment of target lesions, and may reduce radiation during the endovascular procedure. However, the price of the device and its need for contrast infusion limit its routine clinical use.