BACKGROUND: This study investigates the impact of end-stage renal disease (ESRD) on systemic and localized outcomes in peripheral artery disease (PAD) patients following endovascular therapy (EVT), with a focus on major adverse cardiac and cerebrovascular events (MACCEs). METHODS: This retrospective cohort study included symptomatic PAD patients, categorized by the Rutherford classification, who underwent EVT at a single tertiary medical center from May 2018 to May 2021. Patients were divided into ESRD and non-ESRD groups. A propensity score-matched (PSM) analysis was performed to minimize confounding factors. The primary outcome was the occurrence of MACCEs, while the secondary outcome was the incidence of major adverse limb events (MALEs). RESULTS: ESRD patients exhibited significantly worse systemic outcomes, with higher MACCE rates compared to non-ESRD patients in both the entire cohort (79.9% vs. 39.9%; HR: 2.69; 95% CI: 1.80-4.02; p < 0.001) and the matched cohort (HR: 3.88; 95% CI: 2.30-6.53; p < 0.001). They also had higher rates of all-cause mortality and myocardial infarction (MI). For localized outcomes, MALEs were more frequent in the ESRD group in the entire cohort (61.0% vs. 34.9%; HR: 1.84; 95% CI: 1.22-2.76; p < 0.001), but no significant difference was observed in the matched cohort (HR: 1.23; 95% CI: 0.76-1.99; p = 0.40). ESRD was identified as the sole independent predictor of increased MACCE risk (HR: 2.49; 95% CI: 1.65-3.75; p < 0.001). CONCLUSIONS: PAD patients with ESRD face significantly worse systemic outcomes, particularly elevated MACCE rates, after EVT. Preventing MACCEs, especially MI, is essential in this high-risk population. Despite more severe limb conditions, ESRD alone did not significantly increase MALE risk after PSM. CLINICAL TRIAL NUMBER: Not applicable.