Fibrinogen has an important pathophysiological role in tumor cell progression and development of metastases in different types of cancer. The present study aimed to evaluate the role of pre-treatment fibrinogen plasma concentrations as a biomarker for tumor biology and prognosis in patients with uterine leiomyosarcoma (ULMS). Clinical data of patients with ULMS were assessed in this multi-center study Pre-therapeutic fibrinogen plasma concentrations were evaluated. We investigated the association between fibrinogen plasma levels and clinico-pathological parameters and performed univariate and multivariable survival analyses. In total, 70 women with ULMS were included into the analysis. Mean (SD) pre-treatment fibrinogen plasma levels were 480.2 (172.3) mg/dL. Patients with advanced tumor stage, increased tumor size and higher histological grading had higher fibrinogen levels (p = 0.02, p = 0.013, and p = 0.029, respectively). In ULMS patients with increased fibrinogen levels 5-year overall survival (OS) rates were 25.0% compared to 52.9% in ULMS patients with normal fibrinogen, respectively. Univariate survival analyses revealed that elevated fibrinogen plasma levels (p = 0.030), advanced tumor stage (p < 0.001) and undifferentiated histology (p = 0.003) showed association with unfavorable OS. In multivariable analysis, histological grade (p = 0.03) and tumor stage (0.02) were independently associated with survival. Elevated fibrinogen plasma levels were associated with aggressive tumor biology and poor prognosis in women with ULMS. Fibrinogen might be useful as a novel biomarker in ULMS.