Normal hemostasis requires balanced regulation of prothrombotic and antithrombotic factors. Inherited alteration of factor V and prothrombin gene, the G20210A mutation, increases the resistance of factor V to degradation and booster production of prothrombin respectively. These alterations can increase hypercoagulability leading to thrombotic consequences. We aimed to assess the frequencies of these mutations in a group of the population of southern Iran. In total, 198 healthy volunteers with the age range of 1-64 years were selected and screened for factor V Leiden and prothrombin mutations using polymerase chain reaction and restriction fragment length polymorphism techniques. The carrier frequencies for factor V Leiden and prothrombin mutation in the studied cohort were 4.1% and 3.07%, respectively.In the studied area, the allele frequency of factor V is higher than the prothrombin G20210A mutation (0.0204 v 0.0153). According to the data and Hardy-Weinberger equation, the total risk of thrombosis caused by homozygosity and heterozygosity of factor V Leiden, prothrombin G20210A mutation and compound heterozygosity of these mutations are about 1 in 500 individuals.