PURPOSE: Aromatase inhibitors (AIs) are standard therapy for postmenopausal women with hormone receptor-positive breast cancer. However, prolonged AI use is associated with increased cardiovascular (CV) risk, including hypertension, and endothelial dysfunction. This study evaluated the longitudinal changes in endothelial function during AI therapy, and whether AI-induced endothelial dysfunction is reversible post-discontinuation. METHODS: Patients were recruited before or within one month of AI initiation (Pre/early AI), during AI therapy, and after discontinuation (Post-AI) from two prospective studies. Patients with hypertension, hyperlipidemia, diabetes, or tobacco use were excluded. Vascular assessments included peripheral arterial tonometry (EndoPAT) for endothelial function (abnormal if ratio < 1.67) and artery elasticity indices. Estradiol, lipid profiles, and inflammatory markers were also measured. RESULTS: The study included 12 Pre/early AI patients, 67 visits from 41 patients during AI (median 2.89 years on AI), and 9 Post-AI patients (median 4.17 years follow-up). EndoPAT ratio was significantly impaired during AI therapy compared to the Pre/early AI (median: 0.86 vs 2.19). The EndoPAT ratio declined as early as six months and showed a progressive decline over time. Post-discontinuation, the EndoPAT ratio was only partially and not significantly restored (median: 1.08) despite full estradiol restoration and long follow-up. Arterial elasticity showed no significant changes. Systolic blood pressure increased modestly during AI therapy and returned to baseline after discontinuation, while diastolic pressure remained unchanged. Circulating interleukin-6 and tumor necrosis factor-α significantly decreased following AI discontinuation. CONCLUSIONS: AI therapy is associated with significant and progressive endothelial dysfunction, which does not fully recover after treatment cessation, highlighting the importance of CV monitoring in patients receiving long-term AI therapy.