Patients with chronic kidney disease (CKD) have an increased risk for developing peripheral arterial disease (PAD). The aim of this study was to examine the cross-sectional association between novel risk factors and prevalent PAD in patients with CKD. A total of 3,758 patients with estimated glomerular filtration rates of 20 to 70 ml/min/1.73 m² who participated in the Chronic Renal Insufficiency Cohort (CRIC) study were included in the present analysis. PAD was defined as an ankle-brachial index <0.9 or a history of arm or leg revascularization. After adjustment for age, gender, race, cigarette smoking, physical activity, history of hypertension and diabetes, pulse pressure, high-density lipoprotein cholesterol, estimated glomerular filtration rate, and CRIC clinical sites, several novel risk factors were significantly associated with PAD. For example, odds ratios for a 1-SD higher level of risk factors were 1.18 (95% confidence interval [CI] 1.08 to 1.29) for log-transformed high-sensitivity C-reactive protein, 1.18 (95% CI 1.08 to 1.29) for white blood cell count, 1.15 (95% CI 1.05 to 1.25) for fibrinogen, 1.13 (95% CI 1.03 to 1.24) for uric acid, 1.14 (95% CI 1.02 to 1.26) for glycosylated hemoglobin, 1.11 (95% CI 1.00 to 1.23) for log-transformed homeostasis model assessment of insulin resistance, and 1.35 (95% CI 1.18 to 1.55) for cystatin C. In conclusion, these data indicate that inflammation, prothrombotic state, oxidative stress, insulin resistance, and cystatin C were associated with an increased prevalence of PAD in patients with CKD. Further studies are warranted to examine the causal effect of these risk factors on PAD in patients with CKD.