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Introduction: Atherosclerosis causes a chronic reduction of vascularization with consequent impairment of the performance of organs, like the brain or muscles, which determines the functional and cognitive decline of the elderly and their ability to respond to acute stressful condition. Therefore, our aim was to evaluate if ankle brachial index (ABI) could effectively be a determinant of in-hospital functional status and complications in elderly hospitalized patients. Methods: This is a monocentric cross-sectional study of 189 patients aged 65 years or older. The study was undertaken at the Internal Medicine ward of Niguarda Hospital in Milan. ABI (BOSO ABY-System 100) and in-hospital status (activities of daily living, ADL and instrumental activities of daily living, IADL) were collected on the second day of hospitalization. Complications (falls and delirium episodes) were also recorded during the whole hospitalization period. Results: The average age of patients was 79.3 ± 6.9 years. Among outcomes, only ADL (r = 0.192, p = 0.007) and IADL score (r = 0.200, p = 0.005) showed significant correlation with ABI. Moreover, during the subsequent logistic regression, ABI remained among the statistically significant determinants of both scores (β = 0.231, p = 0.013 and β = 0.314, p = 0.001, respectively). Conclusions: The main result of our study is the finding of ABI as a significant determinant of acute in-hospital functional impairment (evaluated as ADL and IADL scores). The continuous exposure of the brain and muscles to the reduced perfusions induced by vascular atherosclerosis, probably determined the reduced ability to respond to stressful conditions. [ABSTRACT FROM AUTHOR]