STUDY QUESTION: What is the effect on ovarian activity of a preceding intake of ulipristal acetate (UPA) when starting a combined oral contraceptive (COC) in the mid-to late-follicular phase of the cycle? SUMMARY ANSWER: This study shows that UPA does not affect the ability of the COC to induce ovarian quiescence. WHAT IS KNOWN ALREADY: UPA is a progesterone receptor modulator that is available for emergency contraception (EC). In theory, UPA could alter the effectiveness of hormonal contraception started immediately following it and vice versa. Current guidelines regarding quick starting a COC following UPA are based on expert opinion only. STUDY DESIGN, SIZE, DURATION: A double-blind, randomized, placebo-controlled trial was conducted at three separate sites, Edinburgh (Scotland), Stockholm (Sweden) and Groningen (the Netherlands), over a 5-month period in 2012. Healthy female volunteers were randomized to take either UPA or an identically packaged placebo, at mid-cycle (once a lead ovarian follicle was determined to be >13 mm on transvaginal ultrasound imaging). Participants were randomized by a computer-generated randomization schedule, allocated by sequential, sealed envelopes. All women then started 21 days of the same COC the following day. The study was designed to show non-inferiority of UPA compared with placebo in terms of the proportion of women attaining ovarian quiescence, as measured by the Hoogland scoring system, while taking COC. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 76 women were recruited over the three sites, Edinburgh (n = 18), Stockholm (n = 13), Groningen (n = 45) and received either UPA (n = 39) or placebo (n = 37). MAIN RESULTS AND THE ROLE OF CHANCE: There were no significant differences in demographic characteristics of women in the UPA and placebo groups. Among the 76 participants treated, 47 (61.8%) reached quiescence and 25 (32.9%) ovulated. There were no significant differences between the groups in the odds ratio (OR) of reaching ovarian quiescence or not; OR 0.97 (95% CI: 0.39-2.46). All women who reached quiescence had done so after taking COCs for 14 days. LIMITATIONS, REASONS FOR CAUTION: The main limitations of the study were that measurements of follicle size and blood tests were performed every 2-3 days and so it was not possible to determine the actual day that follicle rupture occurred for the women who ovulated. Furthermore, the ultrasonography was conducted by a number of investigators at the sites which may introduce error in the form of inter-observer variability in measurements of follicle growth. Finally, the findings of the study cannot be extrapolated to other combined hormonal methods of contraception such as the patch or ring, nor to progestogen-only methods of contraception. WIDER IMPLICATIONS OF THE FINDINGS: This study provides evidence to suggest that UPA does not affect the ability of the COC to induce ovarian quiescence. However, this study design cannot determine whether the COC affects the ability of UPA to delay ovulation. STUDY FUNDING/COMPETING INTEREST(S): Funding was provided by HRA Pharma Paris, France. C.K., S.T.C. and K.G.D. have received funds for conducting research studies and lectures for HRA Pharma. C.K. is director of a contract research organization (Dinox). The remaining authors declare no conflicts of interests.