Obesity is a risk factor for thrombosis-related diseases and a condition that leads to vitamin D deficiency. Furthermore, orthopedic conditions are also at risk for diseases associated with coagulation and endothelial function. This study aimed to assess whether vitamin D supplementation in patients with acute (AOCs) and chronic orthopedic conditions (COCs) and coexisting obesity could affect coagulation and endothelial function. Thirty-three obese individuals with AOCs or COCs were included in the study. Patients were supplemented with vitamin D at 4000 IU/day for 3 months. An enzyme-linked immunosorbent assay (ELISA) was used to measure the concentrations of alpha 2-antiplasmin (α2AP), vascular cell adhesion molecule 1 (VCAM-1), plasminogen activator inhibitor-1 (PAI-1), tissue factor pathway inhibitor (TFPI), and vitamin D, which were examined at two time points-before and after supplementation. Regardless of the increase in serum vitamin D levels in both groups after supplementation, there was a statistically significant increase in VCAM-1 and PAI-1 levels in the group with AOCs, whereas only VCAM-1 increased statistically significantly in the second group. For obese patients with COCs, vitamin D does not appear to have a potentially beneficial effect on coagulation and the endothelium.