The evidence for and against the association of oral contraceptives (OCs) with vascular disease is reviewed, along with the possible pathophysiologic mechanisms for such an association, including effects on coagulation, circulating lipoproteins, and glucose metabolism. The new, low-dose estrogen OCs appear to affect coagulation minimally, and anticoagulant as well as procoagulant effects have been documented. Such concomitant factors as cigarette smoking, obesity, a family history of thrombosis, lack of physical activity, and blood type influence coagulation more strongly. Myocardial infarction and stroke are strongly correlated with the levels and pattern of circulating lipoproteins. The estrogen components of OCs have a favorable effect on lipids, while the effect of progestins, particularly potent androgenic progestins, is unfavorable and could be significant. OCs containing high-dose androgenic progestins can produce abnormal glucose tolerance resulting in increased cardiovascular risk. Low-dose OCs are associated with early, transient breakthrough bleeding. However, educating patients in the management of breakthrough bleeding can help reduce the number of women who must be switched to higher-dose OCs. Epidemiologic evidence confirms the safety of low-dose OCs. By selecting patients carefully, the risk of vascular disease from oral contraception can be reduced to very low levels.