Objective: To determine if a combined oral contraceptive (COC) initiated shortly after ulipristal acetate (UPA) administration interferes with its mechanism of action. Study design: Healthy, reproductive-age women of normal BMI with proven ovulation (serum progesterone >=3ng/mL) were enrolled for 3 cycles (Cycle 1, UPA only; Cycle 2 washout; Cycle 3 UPA plus COC). During Cycles 1 and 3, we monitored subjects with transvaginal ultrasound and blood sampling every other day until a dominant follicle measuring >=15 mm was visualized and UPA (30mg) was administered, which was then followed by daily visits for up to 7 days. In Cycle 3 only, subjects initiated a daily COC (0.15 mg levonorgestrel/30 ug ethinyl estradiol) 2 days after UPA. The study had 80% power to detect a 15% difference in the proportion of cycles with at least a 5-day delay in follicle rupture. We assessed follicle rupture as >50% decrease in size and used hormone values to adjudicate unclear outcomes. Results: A total of 36 women enrolled and 33 completed all study procedures [age 28.4 yr (SD 3.9); BMI 23.4 (SD 2.4)]. Compared to Cycle 1, significantly more subjects demonstrated evidence of follicle rupture in <5 days in Cycle 3 [1/33 (3%) vs. 9/33 (27%), p = .008]. These results include 2 subjects who experienced rupture prior to COC dosing. Conclusion: UPA’s ability to delay ovulation is curtailed by initiating COCs 2 days later.