In this episode, we will discuss all things peripheral arterial disease – definitions, staging, clinical presentation, risk factors, goals of therapy, and guideline-directed medication therapy recommendations including the newest evidence for the use of DOACs. Key Concepts Addressing modifiable risk factors (weight loss, smoking cessation, blood pressure and blood glucose control, dyslipidemia, structured exercise program, etc.) are recommended for the treatment of PAD. Single antiplatelet therapy with either aspirin 81 mg or clopidogrel 75 mg daily are recommended in patients to reduce stroke, MI and other vascular deaths in symptomatic (1A) and asymptomatic patients (IIa- C-EO). Rivaroxaban 2.5 mg BID, when added to aspirin 81 mg daily, is superior to aspirin alone in preventing composite outcome of stroke, MI, and CV death in PAD patients with recent revascularization surgery for PAD but increases the risk of major bleeding. In the absence of heart failure, cilostazol is effective in improving symptoms, quality of life, and increasing walking distance in patients with intermittent claudication.  References Gerhard-Herman MD, Gornik HL, Barrett C, et al. 2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017;135:e686–e725. https://doi.org/10.1161/CIR.0000000000000470 Criqui MH, Matsushita K, Aboyans V, et al. Lower Extremity Peripheral Artery Disease: Contemporary Epidemiology, Management Gaps, and Future Directions: A Scientific Statement From the American Heart Association. Circulation. 2021;144:e171–e191. https://doi.org/10.1161/CIR.0000000000001005 Alonso-Coello P, Bellmunt S, McGorrian C, Anand SS, Guzman R, Criqui MH, Akl EA, Vandvik PO, Lansberg MG, Guyatt GH, Spencer FA. Antithrombotic therapy in peripheral artery disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e669S-e690S. doi: 10.1378/chest.11-2307. PMID: 22315275; PMCID: PMC3278062. Eikelboom JW, Connolly SJ, Bosch J, et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med. 2017; 377:1319-1330. https://www.nejm.org/doi/full/10.1056/nejmoa1709118 Bonaca MP, Bauersachs RM, Anand SS, et al. Rivaroxaban in peripheral arterial disease after revascularization. N Engl J Med. 2020; 382:1994-2004. https://www.nejm.org/doi/full/10.1056/nejmoa2000052