This study was performed in order to establish the role of the prothrombin 20210 G/A and factor V Leiden (R506Q) polymorphisms in the susceptibility to develop venous thromboembolism and early coronary artery disease (CAD). These polymorphisms were determined in 82 consecutive patients with venous thromboembolism, 175 male patients with early CAD, and 200 healthy controls from the same Caucasian population (Asturias, Northern Spain). DNA was amplified using polymerase chain reactions and digested with the appropriate restriction enzymes in order to define the prothrombin and factor V genotypes. The prevalence of the heterozygous for the prothrombin A allele was 3.5% in the general population and 15.8% in patients with venous thrombosis (P = 0.0007); the frequency was 4% in patients with early CAD. No sex-related differences in the prevalence of the A allele were observed, and the average age at the first venous thromboembolic event was similar between GG and AG patients. The frequency of carriers of the factor V Leiden polymorphism was 9.75% among patients with venous thromboembolism, compared with 3.5% among controls, and 3.4% in the patients with CAD. Our data showed an association between venous thromboembolism and the AG genotype at the prothrombin 20210 G/A polymorphism. This polymorphism was not related to an increased risk for early CAD in our population of male patients.