Two coagulation factor polymorphisms, G1691A in the factor V gene and G20210A in the prothrombin gene, are currently the most common known genetic risk factors for venous thrombosis in caucasian populations. Experimental conditions that permit simultaneous determination of these two polymorphisms using PCR-based DNA assays with the restriction enzyme, Hind III, were developed. Moreover, novel PCR-based DNA assays were established using primers that introduce specific cleavage sequences which then permit the simultaneous determination of these polymorphisms using Sac I restriction digestion analysis. Multiplex PCR-based DNA assays were used to analyze a family with a history of venous thrombosis in which these polymorphisms were both present and the results confirm the interesting variability of these genetic risk factors among family members who are symptomatic.