Does ulipristal acetate (UPA) have similar efficacy as emergency contraception (EC) when administered before and after ovulation? The efficacy of UPA-EC was significantly better when administered before than after ovulation. Levonorgestrel (LNG) is effective as EC only when administered before, but not after ovulation. LNG EC taken in the pre-ovulatory and post-ovulatory phase results in shortening and lengthening of the index menstrual cycle, respectively. Whether the same applies to UPA is not known. Prospective, open-label clinical cohort study conducted on 700 women between May 2011 and March 2014. Seven hundred women requesting EC within 120 h after a single act of unprotected sexual intercourse in the index menstrual cycle were recruited at a community family planning clinic in Hong Kong. Each subject received a single oral dose of UPA 30 mg, and 693 of them completed follow-up. Ovulatory status at the time of UPA administration was determined by serum progesterone level supplemented by menstrual history and ultrasound tracking. The main outcome measure was the percentage of pregnancies prevented (PPP). The PPP was significantly higher in subjects who were pre-ovulatory (77.6%) compared with those who were post-ovulatory (36.4%) at the time of UPA administration (P < 0.0001). The observed pregnancy rate following UPA administration was significantly lower than the expected pregnancy rate only in the pre-ovulatory group (P < 0.0001), but not the post-ovulatory group (P = 0.281). The overall failure rate was 1.7% (1.4 versus 2.1% in the pre- and post-ovulatory groups, respectively). Pre-ovulatory administration of UPA resulted in a small delay (median of 3 days), whereas post-ovulatory administration resulted in a minimal advancement (median of 1 day) of the next menstruation, compared with that predicted from previous menstrual pattern. More pre-ovulatory subjects (19.1%) than post-ovulatory subjects (7.8%) had deviation of the next menses of more than 7 days (P < 0.001). The ovulatory status of the subjects was determined based only on menstrual history and a spot sonographic finding together with serum hormonal profile at the time of recruitment. Our findings confirmed comparable efficacy of UPA in the Asian population as in western populations. The comparison between pre- and post-ovulatory use of UPA is a novel finding, which provides insights to its possible pharmacological action. The UPA tablets were provided free of charge by Laboratoire HRA Pharma, who were not involved in the design and execution of the study, or the drafting and final approval of the manuscript. The authors have no other conflicts of interest to declare. The University of Hong Kong Clinical Trials Registry (reference number: HKUCTR-1197).