Lower-extremity peripheral artery disease (LEAD) is associated with increased rates of mortality and morbidity. The aim of this study was to evaluate the associations among inflammatory and thrombotic markers and lower-extremity peripheral disease. A total of 280 patients were enrolled in this study. Of these patients, 152 patients had LEAD on peripheral angiography that was performed because of suspected lower-extremity peripheral disease based on history, physical examination, and non-invasive tests. The control group consisted of 128 patients without LEAD on peripheral angiography. Patients with LEAD were classified according to trans-atlantic inter-society consensus (TASC) II classification. Subsequently, patients in TASC A to B were defined as having mild to moderate peripheral artery disease, and those in TASC C to D were defined as having advanced peripheral artery disease. Thrombotic and inflammatory markers, such as the neutrophil-to-lymphocyte ratio (NLR), the high-sensitivity C (hs-C) reactive protein level, the monocyte-to-high-density lipoprotein-cholesterol ratio, the fibrinogen to albumin ratio (FAR), and whole-blood viscosity at high shear rate (HSR) and low shear rate (LSR), were evaluated in this population. The NLR, the monocyte-to-high-density lipoprotein-cholesterol ratio, the FAR, and whole-blood viscosity, both at a LSR and a HSR, were significantly higher in patients with lower-extremity peripheral disease compared with patients without lower-extremity peripheral disease. We determined that lower-extremity peripheral disease severity was correlated with the NLR, monocyte-to-high-density lipoprotein-cholesterol ratio, FAR, whole-blood viscosity at LSR, and whole-blood viscosity at HSR (r = 0.719, P = .004; r = 0.25, P = .008; r = 0.691, P = .002; r = 0.546, P < .001; and r = 0.448, P = .001, respectively). However hs-C reactive protein levels were similar between patients with or without LEAD (2.47 ± 1.32 1.61 ± 0.91 P = .685). In addition, there was no correlation between the severity of LEAD and hs-C reactive levels. In this study, we determined that the levels of inflammatory and thrombotic biomarkers are elevated in peripheral artery disease, and these levels predict disease severity.