It has been evident for over 30 years that combined oral contraceptive pills (OCP) increase the risk of venous thromboembolism. Recently, it has been suggested that there is an interaction between combined OCPs and the factor V Leiden mutation with the result that the relative risk of venous thromboembolism (VTE) is higher than expected in women who have this heritable thrombophilic defect using combined oral contraceptive pills. In Caucasian populations, factor V Leiden is very prevalent, being present in between 3 and 7% of Europeans and white North Americans. The high prevalence of the defect and its apparent interaction with combined oral contraceptive pills has led to the suggestion that all women should be screened for factor V Leiden prior to commencing contraceptive pills. Although the relative risk of VTE is very significantly increased in factor V Leiden positive women using contraceptive pills, the absolute incidence of venous thrombotic events is low and fatal pulmonary embolism is rare. It would be extremely costly to screen all women for the factor V Leiden mutation and unlikely to be deemed cost-effective. Widespread screening would result in 3-7% of women being denied the most effective and acceptable form of contraception and may influence negotiations with life insurers. It is suggested that only selected women, i.e. those with a personal history of previous venous thromboembolism and those with a clear family history of VTE are offered screening for thrombophilic defects.