Abstract Background Primary mediastinal large B-cell lymphoma (PMBCL) is a rare subtype of diffuse large B-cell lymphoma, arising in the mediastinum. Compression of large mediastinal vessels is common in patients with PMBCL, predisposing these patients to venous thrombosis. The incidence of this complication is still unknown. Materials and methods We conducted a retrospective chart review of 42 consecutive patients diagnosed with PMBCL at a Clinic for hematology, Clinical Center of Serbia between 1999 and 2009 to identify the frequency and risk factors for venous thromboembolic disease (VTE) and its correlation with survival. Results In the subgroup of patients with thrombosis (VTE subgroup) were 15/42 patients (35.7%): 14 patients had deep venous thrombosis and 1 had pulmonary embolism. Ten patients had a thrombosis at the moment of diagnosis PMBCL, while in five thrombosis occurred during the course of the disease. According to hemostasis variables, patients in the VTE subgroup had significantly higher fibrinogen ( P = 0.02) and D-Dimer ( P < 0.001). Also, patients in the VTE subgroup had significantly larger diameter of mediastinal tumor mass ( P = 0.01) and the incidence of syndrome venae cava superior ( P = 0.009). The median survival rate in the VTE subgroup was 45 months (95% CI; 22 to 68 months) while in the NVTE it was 93 (95% CI; 46 to 140 months), (log rank P = 0.058). Conclusions VTE is a common complication in PMBCL patients and according to our results negatively influences survival. Use of antithrombotic prophylaxis may be considered together with chemotherapy, especially in those with bulky mediastinal tumor mass.