Objective. To describe the ultrasonographic and color Doppler ultrasonographic findings in 2 patients with carpal tunnel syndrome associated with a persistent median artery and to report the frequency of this anatomic variation in healthy volunteers. Methods. Two patients with the clinical appearance of carpal tunnel syndrome and 100 wrists and distal forearms of 50 asymptomatic volunteers were examined with ultrasonography and color Doppler ultrasonography. The frequency and size of a persistent median artery and its relationship to median nerve anatomy in the carpal tunnel were evaluated. Results. A large persistent median artery of 3 mm in diameter was found in the affected hands in both patients with carpal tunnel syndrome. Findings were confirmed at surgery. Among the asymptomatic volunteers, a persistent median artery could be found in 13 (26%, 10 [20%] unilateral and 3 [6%] bilateral), with a mean diameter of 1.1 mm (range, 0.5-1.7 mm). In 10 (63%) of 16 hands, the persistent median artery was associated with high division of the median nerve or a bifid nerve configuration in the carpal tunnel. Conclusions. A persistent median artery is a common condition in healthy individuals and in most cases is related to median nerve variations such as high division or a bifid nerve. Because a persistent median artery has a superficial course close to the transverse carpal ligament, preoperative diagnosis of this anatomic variation may be of clinical importance.