This chapter about antithrombotic therapy for peripheral arterial occlusive disease is part of the seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs, and Grade 2 suggests that individual patients’ values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004;126:179S–187S). Among the key recommendations in this chapter are the following: For patients with chronic limb ischemia, we recommend lifelong aspirin therapy in comparison to no antiplatelet therapy in patients with clinically manifest coronary or cerebrovascular disease (Grade 1A) and in those without clinically manifest coronary or cerebrovascular disease (Grade 1C+). We recommend clopidogrel over no antiplatelet therapy (Grade 1C+) but suggest that aspirin be used instead of clopidogrel (Grade 2A). For patients with disabling intermittent claudication who do not respond to conservative measures and who are not candidates for surgical or catheter-based intervention, we suggest cilostazol (Grade 2A). We suggest that clinicians not use cilostazol in patients with less-disabling claudication (Grade 2A). In these patients, we recommend against the use of pentoxifylline (Grade 1B). We suggest clinicians not use prostaglandins (Grade 2B). In patients with intermittent claudication, we recommend against the use of anticoagulants (Grade 1A). In patients with acute arterial emboli or thrombosis, we recommend treatment with immediate systemic anticoagulation with unfractionated heparin (UFH) [Grade 1C]. We also recommend systemic anticoagulation with UFH followed by long-term vitamin K antagonist (VKA) in patients with embolsim [Grade 1C]). For patients undergoing major vascular reconstructive procedures, we recommend UFH at the time of application of vascular cross-clamps (Grade 1A). In patients undergoing prosthetic infrainguinal bypass, we recommend aspirin (Grade 1A). In patients undergoing infrainguinal femoropopliteal or distal vein bypass, we suggest that clinicians do not routinely use a VKA (Grade 2A). For routine patients undergoing infrainguinal bypass without special risk factors for occlusion, we recommend against VKA plus aspirin (Grade 1A). For those at high risk of bypass occlusion and limb loss, we suggest VKA plus aspirin (Grade 2B). In patients undergoing carotid endarterectomy, we recommend aspirin preoperatively and continued indefinitely (Grade 1A). In nonoperative patients with asymptomatic or recurrent carotid stenosis, we recommend lifelong aspirin (Grade 1C+). For all patients undergoing extremity balloon angioplasty, we recommend long-term aspirin (Grade 1C+).