Objective: To determine the effect of the prostaglandin endoperoxide-synthase 2 (PTGS2) inhibitor celecoxib on ovulation and luteal events in women. Study Design: Randomized double-blind crossover design. Ovulatory reproductive-aged women underwent ovarian ultrasound and serum hormone monitoring during four menstrual cycles (control cycle, treatment cycle 1, washout cycle, treatment cycle 2). Subjects received study drug (oral celecoxib 400 mg or placebo) either 1) once daily starting on cycle day 8 and continuing until follicle rupture or the onset of next menses if follicle rupture did not occur (pre-LH surge dosing) or 2) with LH surge and continued for 6 days (post-LH surge dosing). Subjects were randomly assigned to one of the above treatment schemes and received the other in the subsequent treatment cycle. The main outcome was evidence of ovulatory dysfunction. Results: A total of 20 women enrolled and completed the study (Group 1 = 10, Group 2 = 10) with similar demographics between groups. Nineteen subjects exhibited normal ovulation in the control cycle (one had a blunted LH peak). In comparison to control cycles, treatment cycles resulted in a significant increase in ovulatory dysfunction [pre-LH treatment: 30% (6/20), p = 0.04; post-LH treatment: 25% (5/20), p = 0.04]. Peak progesterone, estradiol, and LH levels and luteal phase length did not differ significantly between control and either treatment cycles. Conclusion: Although treatment with celecoxib before or after the LH surge increases the rate of ovulatory dysfunction, most women ovulate normally. Thus, this selective PTGS2 inhibitor appears to be of limited usefulness as a potential emergency contraceptive.