The risk of venous thromboembolism (VTE) in the absence of prophylaxis was evaluated in a retrospective study of 47 women (84 pregnancies) with combined thrombophilia [heterozygous factor V Leiden (FVL) plus prothrombin (FII) 20210A mutation (group I)] and in 82 women (193 pregnancies) with the FII alone (group II). VTE was more frequent in group I than in group II [17.8% versus 6.2%, P = 0.003, relative risk (RR) 2.9, 95% confidence interval (CI) 1.4-5.9], ante partum (7.1% and 2.1%) and post partum (11.5% and 4.2%). The risk was higher in index cases than in family members (RR 2.5, 95% CI 1.2-5.2 and RR 2.1, 95% CI 0.2-22.3 respectively) Even women who had no history of VTE before pregnancy had an increased risk (RR 2.2, 95% CI 1.0-4.8). Our results suggest that, during ante partum, prophylaxis is indicated in women with combined thrombophilia and with a VTE before pregnancy. In those without VTE before pregnancy, prophylaxis might be decided for each individual case, taking into consideration all risk factors. In women with the FII mutation alone, the low risk may not justify prophylaxis in the absence of previous VTE. In post partum, prophylaxis is indicated in all cases.