The coagulation inhibitor potential (CIP) assay may detect major thrombophilia at a sensitivity of 100% and a specificity of 70-80%. Subnormal CIP might be associated with increased risk of thrombosis. This study compared the effect on CIP in plasma samples from postmenopausal women treated with four different regimens. Fibrin aggregation in plasma was monitored after activation with tissue factor. The effect of potentiated inhibition of coagulation was measured. Plasma samples from 202 healthy women randomly assigned to receive treatment for 12 weeks with conventional-dose or low-dose hormone therapy, raloxifene or tibolone were examined. Major thrombophilias were excluded. Compared with baseline, the median level in CIP was reduced by 64% in the conventional-dose group, by 38% in the low-dose group and by 31% in the raloxifene group, whereas for those treated with tibolone the median CIP increased by 9%. The median changes in CIP were significant for both hormone therapy groups (P < 0.0001) and for the raloxifene group (P = 0.003), but not for the tibolone group (P = 0.653). The 12 women with heterozygous factor V Leiden mutation had a significantly reduced median CIP level (P < 0.0001) at baseline. Hormone therapy and raloxifene, associated with venous thromboembolism, reduce the CIP. Tibolone does not reduce the CIP.