Thromboembolic disease is a leading cause of maternal mortality in the United States. Recently, inherited resistance to activated protein C has been recognized as a major risk factor for thrombosis and has been demonstrated in 20–60% of patients with clinically evident thrombosis. The factor V Leiden mutation, which is readily detectable by molecular DNA techniques, is responsible for 90–95% of cases of activated protein C resistance. Because 5% of whites and 1% of blacks in the United States are heterozygous for the Leiden mutation, at least one group has suggested that screening of asymptomatic gravidas for the mutation should be considered. Therefore, we conducted a combined MEDLINE and bibliographic literature search for relevant data and evaluated screening for the factor V Leiden mutation in the context of well-elucidated desirable characteristics for a successful screening program. Based on this evaluation, we conclude that routine antenatal screening for the factor V Leiden mutation cannot be recommended at the present time.