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Abstract: Objective: To evaluate systemic and limb ischemic event rates of PAD patients with prior leg amputation and determine predictors of adverse outcomes. Methods: The REduction of Atherothrombosis for Continued Health (REACH) Registry provided a prospective multinational cohort of 7996 outpatients with PAD enrolled from primary medical clinics in 44 countries in 2003–2004. 1160 patients (14.5%) had a prior leg amputation at any level. Systemic (myocardial infarction [MI], stroke, cardiovascular death) and limb (angioplasty, surgery, amputation) ischemic event rates were determined in a 3-year follow-up. Results: PAD patients with leg amputations on entry had a 5-fold higher rate of a subsequent amputation (12.4% vs. 2.4%, P <.001), lower rate of peripheral angioplasty (8.3% vs. 10.7%, P =.005), and similar rates of surgical revascularization procedures compared with PAD patients without amputation. A nearly 2-fold increase in rates of cardiovascular death (14.5% vs. 7.7%, P <.001) and all-cause mortality (21.8% vs. 12.6%, P <.001) and an increase in the composite outcome of MI, stroke, cardiovascular death, or hospitalization (48.7% vs. 40.0%, P <.001) were noted. Recent (≤1 year) amputation was associated with higher rates of worsening PAD, subsequent lower extremity surgical revascularization procedures, re-amputation, non-fatal MI, and the composite outcome, including hospitalization. Adverse systemic and limb ischemic outcomes were similar regardless of amputation level. Conclusions: Individuals with a history of leg amputations have markedly elevated rates of systemic and limb-related outcomes. PAD patients with recent ischemic amputation have the highest risk of adverse events. A history of “minor” ischemic amputation may confer an identical systemic risk as “major” leg amputation. [Copyright &y& Elsevier]