© The Author(s) 2020.Objective: To examine dynamic thiol/disulphide homeostasis metrics as a novel risk factor of oxidative stress in patients with peripheral arterial disease. Methods: One hundred patients with lower extremity peripheral arterial disease (a study group) and 100 control subjects were included in this prospective case–control study. Participants’ baseline clinical characteristics and laboratory data including some oxidant/antioxidant status parameters such as albumin, ferroxidase and myeloperoxidase, and thiol/disulphide homeostasis parameters such as native thiol, total thiol and disulphide, as well as native thiol/total thiol, disulphide/native thiol and disulphide/total thiol ratios were all recorded and then compared between the groups. Results: Mean albumin and ferroxidase, and median myeloperoxidase levels were found to be significantly higher in patients with the peripheral arterial disease than in control group (p = 0.045, p = 0.000 and p = 0.000, respectively). Mean native thiol and total thiol, and median disulphide levels were found to be significantly lower in the study group as compared with the control group (p = 0.000, p = 0.000 and p = 0.037, respectively). According to the results of logistic regression analysis, systolic blood pressure, ferroxidase and myeloperoxidase levels were detected to be the independent predictors of peripheral arterial disease. Conclusion: Our report is the first one in the literature investigating dynamic thiol/disulphide homeostasis metrics as a novel risk factor of oxidative stress in peripheral arterial disease. Dynamic thiol/disulphide homeostasis metrics may be used as a valuable risk factor of oxidative stress in patients with the peripheral arterial disease since it is readily available, easily calculated and relatively cheap.