Cystic adventitial disease (CAD) of the popliteal artery is a rare vascular disorder in which a mucin-containing cyst develops in the adventitial layer of the artery. We report two such cases, each of which was treated differently. The first case was of a 49-year-old man, treated by excision of the involved arterial segment and interposition of an autologous saphenous vein graft. The second case was of a 36-year-old man, treated by local excision of the affected arterial segment and interposition with prosthetic bypass grafting. Both patients presented with rapidly progressing intermittent claudication of the lower extremities, but without remarkable evidence of atherosclerotic disease. Physical examination revealed diminished or absent popliteal, posterior tibial and dorsalis pedis pulses in the lower extremities. Color Doppler ultrasound of the popliteal artery revealed hypoechoic cystic lesions surrounding the vessel, and popliteal arterial stenosis, in both patients. Surgery resulted in immediate improvement of the arterial pulse distal to the lesion. Both patients recovered uneventfully. Thus, resection of the involved artery segment and interposition bypass grafting, using either patient or prosthetic veins, offers favorable results for CAD of the popliteal artery.