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The aim of this study was to help understand the different outcomes when treating peripheral arterial disease (PAD) versus coronary artery disease (CAD). We compared plaque morphology between PAD and CAD using intravascular ultrasound.Complete Lesion Assessment with ffR and IVUS TechnologY (CLARITY) was a prospective, multicenter trial that enrolled 50 PAD patients with a lower extremity wound fed by a tibial or a peroneal artery with diameter stenosis more than 50%. Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents (ADAPT-DES) was a prospective, multicenter, registry that enrolled 8582 CAD patients. We compared preintervention intravascular ultrasound findings in 42 PAD lesions from CLARITY versus 79 matched CAD lesions from ADAPT-DES.Compared with CAD lesions, PAD lesions had (i) smaller mean vessel, plaque, and lumen volumes; (ii) twice the lesion length; (iii) greater maximum superficial calcium arc and plaque eccentricity (i.e. there was more concentric plaque) measured at the minimum lumen area site; (iv) calcium arc and plaque eccentricity were positively correlated to plaque burden in both PAD and CAD lesions; and (v) calcium arc and the presence of concentric plaque were greater in PAD compared with CAD independent of the degree of plaque burden.Compared with CAD lesions, PAD lesions in a tibial or a peroneal artery were longer; had more concentric, diffuse, and calcified plaque; and had smaller vessel volumes.