Background: Infertility is the inability of a sexually active couple with no contraception to achieve natural pregnancy within one year. Unexplained female infertility should be a term used when the female reproductive system has been evaluated according to current agreed standards, and no abnormalities are detected. Clomiphene citrate (CC) has been used as a first-line ovulation induction agent. Aromatase inhibitors are new groups of drugs for fertility treatment. Letrozole is an orally-active aromatase inhibitor, with good potential for ovulation induction. Objective: This study compared the effect of clomiphene citrate and letrozole in induction of ovulation in the treatment of infertility. Patients and methods: This prospective randomized controlled study was conducted at Obstetrics and Gynecology Department, Al-AzharUniversityHospitals and Al-AhrarHospital (ministry of health) on 100 women between 20 - 35 years old having unexplained infertility. Patients were divided into two equal groups: Letrozole group received 5 mg of letrozole orally daily from day 3 to day 7 of menses, and CC group, women received 100 mg of clomiphene citrate orally once daily from day 3 to day 7 of the menses and for up to three menstrual cycles. Results: There was a significant increase of positive pregnancy test in letrozole group compared to clomiphene group.There was a significant difference in multiple pregnancy rate and high significant differences in Doppler flow indices between letrozole group and clomiphene group. Conclusion:Letrozole has a better ovulation rate with better follicular development and higher pregnancy rate, CC group has less effect on the endometrial thickness and side effects.