BACKGROUND Minimally invasive imaging techniques are increasingly used for clinical decision making in patients with peripheral arterial occlusive disease (PAOD). OBJECTIVE To assess whether gadofosveset-enhanced three-dimensional (3D) magnetic resonance (MR) angiography could replace digital subtraction angiography (DSA) for the evaluation of lower-extremity PAOD. METHODS Thirty patients with symptomatic PAOD underwent prospectively both MR angiography and DSA. Gadofosveset-enhanced 3D MR angiography was performed on a 1.5T system equipped with a peripheral angio matrix coil. Four blinded observers independently analyzed MR angiograms and DSA images. The lower arterial vascular system was divided into three anatomic segments (aortoiliac, femoropopliteal, infrapopliteal) for review. The status of each segment was graded as normal, stenosis less than 50%, stenosis greater than 50%, or occluded and/or aneurismatic. Principal and secondary lesions were reported. RESULTS Although interobserver agreement for both was excellent, it was higher for DSA (kappa=0.92) than for MR angiography (kappa=0.86) for reporting the principal and secondary lesions in all segments. For different anatomic locations, the interobserver agreement of MR angiography and DSA was as follows: aortoiliac (kappa=0.93, k=0.95), femoropopliteal (kappa=0.86, k=0.90), and infrapopliteal (kappa=0.78, k=0.85). The lowest agreement was found for MR angiography on infrapopliteal segments (kappa=0.78). In four (13.3%) cases, MR angiography showed lesions that were not found by DSA. Five (16.6%) aneurysm cases, not observed by DSA, were shown by MR angiography. CONCLUSIONS Gadofosveset-enhanced 3D MR angiography can be proposed for first-line imaging in the management of lower-limb PAOD patients and permits the selective use of DSA as a second-line examination when MR angiography fails or in an endovascular approach.