We studied 30 control women and 131 pill users to evaluate effects of birth control pills and clinical factors on hemostasis. When control patients were matched with an equal number of pill users, none of the direct markers of activated hemostasis (fibrinopeptide A, platelet factor 4, and beta thromboglobulin) were increased. Plasminogen, prekallikrein, and protein C (protective against clotting) were significantly higher in pill users. Fibrinogen, antithrombin, alpha-2 antiplasmin, and fibronectin were comparable. Among the 131 pill users, antithrombin levels decreased with a family history of thromboembolism. Fibrinogen and fibronectin were increased with obesity, but there was no evidence of activated hemostasis. Overall, pill use did not appear to result in hypercoagulability. Considering family history of thromboembolism might further improve the safety of oral contraceptive use.