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Introduction:Peripheral artery disease (PAD) has been shown to be related to worse outcomes after percutaneous coronary intervention (PCI). Little is known about the prognostic impact of PAD in patients with concomitant high bleeding risk (HBR) undergoing PCI.Hypothesis:The aim of this study was to assess ischemic and bleeding complications at 1 year after PCI in HBR patients with or without concomitant PAD. We hypothesized that in HBR patients with PAD, the risk of ischemic and, to a lesser extent, bleeding complications would be higher than in non-PAD patients.Methods:Consecutive patients undergoing PCI with drug-eluting stent implantation (DES) at a large tertiary-care center (Mount Sinai Hospital, New York, USA) between 2012 and 2019 and fulfilling the Academic Research Consortium HBR criteria were included. The primary outcome was major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction (MI) and stroke 1 year after PCI. The key secondary outcome was major bleeding, according to a study specific definition.Results:Out of 7,192 HBR patients, 975 (13.6%) had concomitant PAD. Compared to non-PAD patients, PAD patients were more likely to have cardiovascular risk factors and comorbidities and to undergo a complex PCI. MACE occurred in 93 (11.4%) patients with PAD and 382 (7.3%) without PAD. The increased risk of MACE (HR 1.59, 95% CI 1.27-1.99, p<0.001) was mainly driven by an excess of all-cause death and MI in PAD patients (Figure 1). Bleeding was observed in 80 (8.5%) PAD and 410 (6.9%) non-PAD patients (HR 1.25, 95% CI 0.98-1.59, p=0.066).Conclusions:Among HBR patients undergoing PCI with DES implantation, PAD was associated with a higher risk of MACE and a borderline increase in bleeding events.