We report the prevalence of Factor V Leiden (FVL) in European American and African American patients on warfarin therapy residing in Alabama. Methods.: Detailed history was obtained and FVL genotype was determined for 288 patients enrolled in a prospective cohort: Pharmacogenetic Optimization of Anticoagulation Therapy. Racial differences in genotype frequency were assessed by the Chi-square statistics and HWE assumptions by G-statistics. Race-specific analysis for the association between site of thromboembolism and the presence of FVL mutation was assessed using logistic regression. Results.: The overall heterozygote (GA genotype) frequency was 4.9%. No patient was found to be homozygous (AA) for the variant allele. The prevalence of GA was higher in European American (8.6%) compared to African American (1.4%) patients (p = 0.004). The FVL genotype frequency was significantly different across race for venous thromboembolic events (p = 0.014) but not for arterial thromboembolic events (p = 0.20). Multivariable race-specific analysis highlights the contribution of FVL mutation to the risk of venous thromboembolic events in European American (p = 0.03) but not in African American patients (p = 0.95). European American patients with the GA mutation were approximately 6.3 times more likely to have experienced a venous, rather than arterial thromboembolic event. Conclusion.: In Alabama, among patients on warfarin, the GA genotype is more prevalent in European Americans compared to African Americans. In European Americans, but not in African Americans, the GA genotype was more prevalent in patients with venous compared to arterial thromboembolic events. © 2006 Elsevier Inc. All rights reserved.