Background: Letrozole is an aromatase inhibitor which has been proposed as a great tool in ovulation induction and infertility management. This study aimed to evaluate whether the use of letrozole in combination with gonadotropins and GnRH antagonist is superior to gonadotropins and GnRH antagonist alone in women undergoing ICSI treatment. Methods: This prospective randomized controlled trial was conducted during the period from October 2017 to March 2020 in a private fertility center. 112 participants were randomly allocated into two groups either intervention (Letrozole plus antagonist protocol) or control (antagonist protocol) groups. Participants were subjected to ovarian stimulation (OS) using a GnRH antagonist protocol. Only for the intervention group, letrozole was added from the second day of the cycle to the sixth day. On the day of hCG trigger, endometrial thickness, estradiol and progesterone level were assessed. The results were correlated to the outcomes of the Intracytoplasmic sperm injection (ICSI) cycle. Results: Both the intervention and control groups were balanced in respect to the demographic and clinical characteristics. The stimulation outcomes were comparable between the two studied groups. The clinical pregnancy rate and the ongoing pregnancy rate were comparable between both groups. There was no significant relation between the day of embryo transfer and either occurrence of clinical pregnancy or ongoing pregnancy among both groups' participants. Conclusions: Letrozole co-treatment in the first five days of gonadotropins stimulation in anatagonist cycles did not show any significant change in the pregnancy outcomes of ICSI cycles.