<p>Patients with myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF), are at increased risk of atherosclerosis, including peripheral arterial disease (PAD). Critical limb ischemia (CLI) may complicate PAD and is associated with significant mortality and morbidity. Despite the increased risk of thrombosis with MPN, outcomes of CLI in MPN patients are unclear. We conducted an analysis utilizing the 2017–2020 National Readmission Database (NRD) of patients hospitalized for CLI with and without MPN. Patients with MPN were propensity score matched (PSM) with patients without MPN. Primary outcome was composite outcome of major adverse cardiovascular and limb events (MACLE). Logistic regression was utilized to estimate risk of MACLE in patients with MPN vs. without MPN. Inverse-probability treatment weighted (IPTW) analysis was performed to evaluate the effect of revascularization on MACLE in patients with MPN. A total of 102,598 patients were included, 931 (0.9%) had MPN. After PSM, MPN was associated with increased risk of MACLE (47.3% vs. 39.1%; OR 1.40, 95% CI 1.21–1.62). After IPTW, revascularization was associated with decreased risk of MACLE among patients with MPN (45.0% vs. 50.7%; OR 0.80, 95% CI 0.66–0.96). Among patients admitted with CLI, MPN was associated with increased risk of MACLE especially ET and MF phenotypes. Revascularization was associated with decreased risk of MACLE among patients with MPN. Further investigation is needed in order to improve outcomes in patients with MPN and CLI.</p> Graphical Abstract <p></p>