D-dimer and fibrinogen are nonspecific diagnostic biomarkers for venous thromboembolism (VTE). The aim of this article was to present the values of D-dimer and fibrinogen in relation to the anatomical localization of deep vein thrombosis (DVT). This was an observational study, which included 1,142 patients hospitalized from 2010 to 2019 at the Department of Angiology, Clinical Center University of Sarajevo. Data on gender, age, and thrombosis location were collected of all patients. Fibrinogen and D-dimer values were available for 983 and 500 patients, respectively. Thrombosis location was classified as iliofemoral (521–45.6% patients), femoral–popliteal (486–42.6% patients), isolated calf DVT (63–5.5% patients), and upper extremity DVT (UEDVT in 72–6.3% patients). A majority, 448 (89.6%), of patients had high D-dimer (the cutoff is 0.55 mg/L) and 662 (67.3%) patients had high fibrinogen (reference range: 1.8–3.8 g/L).The highest D-dimer was detected in patients with iliofemoral DVT (mean: 10.48 mg/L), χ2 = 50.78, p = 0.00. The highest fibrinogen was detected in patients with iliofemoral DVT as well (mean 4.87 g/L), χ2 = 11.1, p = 0.01. D-dimer and fibrinogen values are significantly higher in patients iliofemoral DVT than femoral–popliteal and isolated calf DVT, and D-dimer values are significantly higher in lower extremity DVT than UEDVT, but these biomarkers cannot be used alone to discriminate between thrombosis locations. Further imaging is required.