Intrauterine devices (IUDs) that release progestins are highly effective contraceptives, but they induce breakthrough bleeding that some women find unacceptable. Because progesterone (P) antagonists (AP) are known to suppress the endometrium, induce amenorrhea, and inhibit fertility, AP IUDs may provide an effective contraceptive that also controls endometrial bleeding. Here we assessed the effects of empty (blank) vs AP-releasing (ZK 230 211) IUDs on bleeding patterns and endometrial growth in ovariectomized, artificially cycled macaques. The AP IUDs (but not the blank controls) induced extended, frank menstruation when inserted during the late luteal phase, an indication of local AP action. Over time, endometrial glandular and arterial proliferation were inhibited, steroid receptors were elevated, spiral arteries showed degenerative changes, progesterone withdrawal bleeding was prevented and estradiol-dependent proliferation was suppressed by the AP IUDs. In sum, AP IUDs suppressed the effects of P on endometrial progestational development and blocked the effects of estradiol on endometrial proliferation as previously shown for systemic treatment with APs. Therefore, AP IUDs may provide novel contraceptive devices with minimal breakthrough bleeding.