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Patients with widespread atherosclerosis such as peripheral artery disease (PAD) have a high risk of cardiovascular and limb symptoms and complications, which affects their quality of life and longevity. Over the past 2 decades there have been substantial advances in diagnostics, pharmacotherapy, and interventions including endovascular and open surgical to aid in the management of PAD patients. To summarize the evidence regarding approaches to diagnosis, risk stratification, medical and intervention treatments for patients with PAD, guided by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework, evidence was synthesized, and assessed for quality, and recommendations provided-categorized as weak or strong for each prespecified research question. Fifty-six recommendations were made, with 27% (15/56) graded as strong recommendations with high-quality evidence, 14% (8/56) were designated as strong recommendations with moderate-quality evidence, and 20% (11/56) were strong recommendations with low quality of evidence. Conversely 39% (22/56) were classified as weak recommendations. For PAD patients, strong recommendations on the basis of high-quality evidence, include smoking cessation interventions, structured exercise programs for claudication, lipid-modifying therapy, antithrombotic therapy with a single antiplatelet agent or dual pathway inhibition with low-dose rivaroxaban and aspirin; treatment of hypertension with an angiotensin converting enzyme or angiotensin receptor blocker; and for those with diabetes, a sodium-glucose cotransporter 2 inhibitor should be considered. Furthermore, autogenous grafts are more effective than prosthetic grafts for surgical bypasses for claudication or chronic limb-threatening ischemia involving the popliteal or distal arteries. Other recommendations indicated that new endovascular techniques and hybrid procedures be considered in patients with favourable anatomy and patient factors, and finally, the evidence for perioperative risk stratification for PAD patients who undergo surgery remains weak., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)