BACKGROUND: The prevalence of venous thromboembolism (VTE) and the impact of blood coagulation factors on the occurrence of VTE in the general population have been rarely studied. METHODS: In the KORA-Fit (S4) study with n = 805 participants (53% females) with a mean age of 62.4 (SD 5.7) years, the prevalence of physician-diagnosed VTE was assessed during a face-to-face interview. Plasma concentrations of antithrombin, fibrinogen, factor VIII, D-dimer, protein C, and protein S activity were analyzed; additionally, aPTT and prothrombin time were assessed as screening tests. The associations between coagulation factors and VTE were analyzed using multivariable logistic regression models. Non-linear associations were explored using restricted cubic splines. RESULTS: The self-reported prevalence of VTE was 3.2%. The blood coagulation factors examined did not differ between individuals with and without VTE, except for factor VIII. In multivariable analyses, protein C (adjusted p = 0.008), protein S (adjusted p = 0.008), and aPTT (adjusted p = 0.016) were non-linearly inversely associated with VTE. CONCLUSIONS: Our findings in a middle-aged and elderly population demonstrate significant associations between specific blood coagulation factors and the prevalence of VTE. However, these hypothesis-generating findings must be confirmed in prospective cohort studies. Also, research on the complex interactions between coagulation factors and patient-specific risk factors in the pathogenesis of VTE is warranted.