Factor V(Leiden) is the most common abnormality detected in patients examined because of hereditary thrombophilia. The most widely used clot-based screening test is based on the activated partial thromboplastin (aPTT) time. This test has a low sensitivity. A comparison of the aPTT-based test with a Russell viper venom time test (RVVT) was performed in matched samples. All samples were analyzed by polymerase chain reaction (PCR) for the factor V(Leiden) defect. We studied 139 samples, of which 109 were PCR-negative; 30 were PCR-positive. Using the manufacturer's suggested threshold ratio of 2, the aPTT test showed a sensitivity of 0.43, a specificity of 0.86, and a positive predictive value (PPV) of 0.97. The RVVT test had a sensitivity of 1.0, a specificity of 0.95, and a PPV of 0.91. Segregation of a subpopulation of this study population into ABO group O vs non-group O showed an effect of ABO group on the aPTT test but not on the RVVT test, consistent with an influence of factor VIII clotting (factor VIII:C) on the aPTT test. The RVVT test seems superior to the unmodified aPTT test as a screening test for factor V(Leiden).