SummaryBackground: Patients with peripheral arterial disease (PAD) represent a high-risk patient subset in the setting of non-STsegment elevation acute coronary syndromes (NSTE ACS). The efficacy and safety of early invasive management for such patients remains unclear.Hypothesis: Early invasive management would be well tolerated and effective among patients with NSTE ACS and PAD.Methods: Patients from the Treat angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis In Myocardial Infarction (TAC-TICS-TIMI) 18 trial were stratified by the presence or absence of PAD and assessed with respect to baseline clinical factors. The outcomes of patients with PAD and NSTE ACS were examined with respect to treatment assignment to either early invasive therapy or conservative treatment of NSTE ACS. Finally, the bleeding and stroke rates of patients with PAD managed invasively were compared with patients with PAD managed conservatively.Results: Of 2,219 patients with NSTE ACS overall, 166 (7.5%) had concomitant PAD. Compared with those patients without PAD, those with PAD were older (75 vs. 62 years, p < 0.001) and were more likely to have high-risk clinical features, including prior histories of bypass surgery (39 vs. 20%,