(1) Background: Thromboangiitis obliterans or Winiwarter-Buerger disease (WBD), is an inflammatory, thrombotic occlusive, peripheral vascular disease, usually occurring in young smokers. The pathophysiological mechanisms underlying the disease are not clearly understood. The aim of this study is to investigate the imbalance between oxidants and antioxidants occurring in these patients. (2) Patients and Methods: In this cross-sectional study, 22 male patients with WBD and 20 healthy male smoking habit matched control group were included. To evaluate the possible sources of oxidative stress, the antioxidant biomarkers, and the markers of lipid peroxidation and protein oxidation, serum samples were analyzed for total oxidative status (TOS), total antioxidant capacity (TAC), myeloperoxidase (MPO), coenzyme Q10 (CoQ10), superoxide dismutase (SOD), glutathione reductase (GR), malondialdehyde (MDA), and protein carbonyl (PC) activity and/or content. (3) Results: The circulating levels of TOS, TAC, and CoQ10 were significantly higher in WBD patients, with respect to healthy smokers as controls. No significant difference was found among the serum level of PC, total cholesterol, MPO, and GR activity in WBD patients and healthy smoker controls. The activity of SOD and the mean serum level of MDA were significantly lower in WBD patients, with respect to healthy smoker controls. (4) Conclusion: Considerably high levels of oxidative stress were detected in WBD patients, which were greater than the antioxidant capacity. The low level of MDA may be associated with the enzymatic degradation of lipid peroxidation products. High levels of CoQ10 and low levels of SOD may be related to a harmful oxidative cooperation, leading to the vasoconstriction of WBD, representing a promising tool to discern possible different clinical risks of this poorly understood peripheral occlusive disease.