Background: Peripheral arterial disease (PAD) is a common risk factor for mortality in hemodialysis (HD) patients. Pentraxin-3 (PTX3), an inflammatory mediator, is widely expressed in peripheral tissues and may have a predictive value for PAD. Objective: To evaluate the role of plasma PTX3 as a predictor for PAD in maintenance HD patients. Patients and Methods: 84 subjects were included; Group 1: 42 End-stage renal disease (ESRD) patients on maintenance HD, and Group 2: 42 Healthy controls. After history taking, examination, and routine laboratory investigations, the following was done; Assessment of lower limb arteries by Color and Pulsed Doppler Ultrasound, ankle-brachial index (ABI), measurement of high-sensitivity C-reactive protein (HS-CRP), and plasma Pentraxin-3 (PTX3) by ELISA. Results: The ABI in HD patients (0.67 ± 0.13) was significantly lower than controls (1.1±0.16), (P<0.001). HS-CRP levels in ng/ml in HD patients (10.5 ± 2.3) were significantly higher than controls (1.48 ± 0.34), (P<0.001). Plasma PTX3 levels in ng/ml in HD patients (6.87 ± 1.36) were significantly higher than controls (1.47 ± 0.25), (P<0.001). Plasma PTX3 had a significant negative correlation with ABI, and Hb% (P<0.001), and a significant positive correlation with cholesterol and triglycerides (P<0.001), whereas HS-CRP did not have correlation with ABI. Plasma PTX3 at a cutoff of 2.35 ng/ml showed a higher predictive value for PAD than HS-CRP at a cutoff of 2.25 ng/ml regarding sensitivity (95.2% vs 88.1%), and specificity (92.0% vs 86.7%) respectively, (P<0.001). Conclusion: Plasma PTX3 maybe used as a predictor for PAD in maintenance HD patients, with a high sensitivity and specificity.