The StarClose (Abbott Vascular, Redwood City, CA) arterial closure device utilizes an extraluminal nitinol clip to establish hemostasis. The purpose of this study was to determine the safety and efficacy of StarClose from a prospective peripheral arterial disease (PAD) registry. Over an 18-month time interval, 500 StarClose devices were used in 378 consecutive patients with symptomatic PAD after diagnostic and/or therapeutic endovascular cases. Patient demographics along with objective criteria including duplex ultrasound images, common femoral artery flow velocities, and ankle-brachial indexes (ABIs) were analyzed before and after StarClose placement. All outpatients received prophylactic antibiotic (one dose), periprocedural heparin (without protamine reversal), and antiplatelet therapy. Aspirin and clopidogrel (Plavix) was used for all patients undergoing therapeutic intervention. There were 378 patients who underwent procedures for aortoiliac or infrainguinal PAD, 99 of which were bilateral. Of the 500 arteriotomy closures, 296 were therapeutic interventions with sheath sizes of 6-8 F in the common femoral artery. The diagnostic studies (n = 204 arteriotomies) were performed with a 5F sheath. The technical success in achieving hemostasis was 97.2%; only 14 devices had a deployment problem requiring prolonged manual compression. Median length of stay was 157 min for patients done on an outpatient basis. Eleven of 260 (4.2%) on duplex follow-up had a doubling of the peak systolic velocity, only one of which was symptomatic. Late follow-up showed 42 of 360 (11.7%) with a drop in ABI >0.10. Nine major complications (2.0%) were identified in follow-up. The StarClose closure device has a low major complication rate and is safe and efficacious in patients with PAD, although stenosis at the arteriotomy site may occur. The device has achieved rapid hemostasis without need for anticoagulant reversal and requires significantly less time to ambulation than manual compression.