Background:Hemodialysis patients are at a higher risk of developing peripheral artery disease (PAD) than the general population. However, factors associatedwith the incidence or progression of PAD in hemodialysis patients have not been fully elucidated. Furthermore, very few studies have assessed the associationbetween the development of PADandphysical activity levels, although most of hemodialysis patients have low levels of daily physical activity and are thus prone to arteriosclerosis. Purpose: The purpose of this study was to examine whether physical activity levels contribute to the development of PAD in hemodialysis patients using multivariate analyses adjusted for clinical variables. Methods: This prospective study followed Japanese outpatients undergoing maintenance hemodialysis three times a week at the Hemodialysis Center from July 2012 to January 2013 for one year. Patients who had been treated with percutaneous transluminal angioplasty and/or stenting, had an ankle-brachial index (ABI) ≥1.40 at baseline, had noncompliance with prescribed medications (antiplatelet and statin drugs), and showed changes in physical activity levels during the observation period due to adverse clinical events were excluded. Age, sex, body mass index, dialysis vintage, history of smoking, comorbid conditions, blood biochemical data (creatinine, calcium-phosphate products, low and high-density lipoprotein cholesterol, triglyceride, and intact parathyroid hormone), levels (high or low) of physical activity, and ABI were obtained from clinical records at baseline. Patients were classified as having a low physical activity level if they used wheelchair at home/hospital, required walking assistance, or had limited ambulation at/around home. For analysis, patients were divided into groups with or without newly diagnosed PAD (ABI ≥1.00 at baseline and ABI ≤0.99 at the endpoint), and with or without progressive PAD (ABI ≤0.99 at baseline and subsequent decrease in ABI to ≥0.10) according to changes in ABI during the study period. Multivariate logistic regression analyses adjusted for baseline clinical variables were performed to identify the prognostic effect of physical activity levels on PAD incidence or progression after one year. Analysis was performed using the Statistical Package for Social Sciences (SPSS version 21, USA). Results: A total of 124 eligible Japanese outpatients (mean age, 65.7± 10.7; male, 52.4%; mean hemodialysis vintage, 9.9± 8.6 years) were included in the study. During the follow-up period, 13 hemodialysis patients (10.5%) were newly diagnosed or had progressive PAD. Adjusted multivariate logistic regression analyses revealed a significant association between PAD incidence or progression and physical activity levels (odds ratio, 5.504; 95% confidence interval, 1.653–18.326; P= 0.005). Conclusion(s):Decreased physical activity is closely and independently associated with an increased incidence or progression of PAD in hemodialysis patients. Implications: Hemodialysis patients reportedly have significantly lower physical activity levels compared to age-matched community-dwelling people. Regular physical therapy to increase habitual physical activity should be considered as an effective approach to prevent the development of PAD in clinically stable hemodialysis patients.