Abstract Study question Are GnRH-antagonist and progestin-primed ovarian (PPOS) stimulation protocols comparable in terms of effectiveness and efficiency in an egg donor program? Summary answer The PPOS protocol would have similar efficacy to the antagonist protocol, despite a slightly lower rate of useful blastocyst, without impact on recipient’s clinical results. What is known already There are numerous studies based on the comparison of oral progestin (P) vs. subcutaneous GnRH-antagonist (A) as pituitary suppressors during ovarian stimulation with gonadotropins, showing similar results in terms of ovarian response and reproductive outcomes in IVF cycles. Limited data are available on the comparison of both protocols in egg donor programs to evaluate their effectiveness and efficiency. Study design, size, duration Retrospective and observational cohort study with 711 oocyte donor cycles included over 18 months (July 2022-Dec 2023). As pituitary suppressors during ovarian stimulation, Ganirelix was used in 394 cycles and Medroxyprogesterone in 317. We obtained 626 reception cycles (369 from A group and 257 from P group). 499 egg-recipients underwent an embryo transfer (309 form A group and 190 from P group). Live birth rates were calculated only over the 192 informative embryo transfer cycles. Participants/materials, setting, methods Variables such as duration of the ovarian stimulation, number of mature oocytes (MII), maturation rate, fertilization rate, useful blastocysts (uBL) rate and their quality (>3BB/≤3BB), clinical pregnancy and live birth rate, have been evaluated. An economic analysis has been conducted for both protocols. Statistical analysis was performed using T-Student and Chi-Square tests. Main results and the role of chance There were no significant differences between groups A and P in terms of: average stimulation days (11.44±1.45 vs. 11.39±1.38, p = 0.62), average number of MII (15.69±7.46 vs. 15.12±7.12, p = 0.30), maturation rate (78.97% vs. 80.01%, p = 0.13), and fertilization rate (68.6% vs. 70.1%, p = 0.15). However, a statistically significant difference was observed in the rate of viable blastocyst formation (uBL/2PN) between groups A and P (70.4% vs. 66.8%, p < 0.05), although there were no differences in embryo qualities obtained (>3BB: 89.4% vs. 90.6%, ≤3BB: 10.6% vs. 9.1%, p = 0.083). Regarding obstetric outcomes, no differences have been found in live birth rates between the two groups (52,4% vs 64,5%, p = 0,11). The cost of the antagonist protocol was significantly higher being 8.48% more expensive than the oral progestin protocol (p < 0.05). Limitations, reasons for caution A regulated randomization has not been used to assign donors to both treatments. The population size, although enough to provide significant differences, could be wider. The number of cycles performed with P are smaller compared to A. Most clinical pregnancy are still ongoing so these data are lacking Wider implications of the findings Besides being more donor-friendly, the progestin-primed ovarian stimulation offers a significant economic advantage. Both protocols have proven similar efficacy. Clinical data are necessary to evaluate the impact of the lower BLu rate on the reproductive outcomes. Trial registration number Not applicable