Background: Determining the initiation day of antagonist administration is an important and challenging issue and different results have been reported in the previous studies. The present study was designed to compare the controlled ovarian hyperstimulation (COH) cycles outcomes of the early start of gonadotropin-releasing hormone antagonist (GnRH-ant) protocol with conventional flexible GnRH-ant protocol in patients with poor ovarian response (POR) diagnosis. Methods: This randomized controlled trial was performed on infertile women who were diagnosed as poor ovarian responder in IVF/ICSI cycles at Arash Women’s Hospital affiliated to Tehran University of Medical Sciences between September 2019 and May 2020. POR was defined according to the Bologna criteria and the eligible women were randomly allocated into an experimental (early onset GnRH-ant) and control (flexible GnRH-ant) groups. The women in the experimental group received recombinant gonadotropins (150-225 IU) and GnRH-ant (0.25 mg) simultaneously on the second day of the cycle. In control group, the starting and dose of gonadotropins were similar but daily administration of GnRH-ant was initiated when the leading follicle diameter was ≥ 13 mm. The IVF/ICSI outcomes were compared between groups.Results: Totally, 116 women were randomly assigned to early start antagonist group (n=58) and control group (n=58). The analysis showed that the two groups did not have a statistically significant difference in terms of the ovarian stimulation duration and the total dose of used gonadotropins. Although, the total number of MII oocytes in early start of antagonist group was significantly higher than that of in control group (P=0.04). In the following, clinical and ongoing pregnancy rates per ET in early start of antagonist group were significantly higher than those of in control group (P=0.02 and P=0.03, respectively); however, the implantation and miscarriage rates were similar between group.Conclusion: The early onset of GnRH-ant protocol can improve the number of retrieved and MII oocytes rates and probably the pregnancy outcome after fresh embryo transfer in POR patients; however, larger randomized clinical trials are required to compare the pregnancy outcomes after this approach with other COH protocols with considering cost-effectiveness issue.Trial registration: IRCT, IRCT20110731007165N9. Registered 8 February 2020 – Registered while recruiting, https://www.irct.ir/trial/45024.