This study was set to evaluate conception rate of five days intravaginal nonsteroidal aromatase inhibitor (letrozole), combined with PGF2α injection at day of removal of sponges. In comparison with standard GPG protocol for estrus synchronization. A total of twenty healthy, cyclic non lactating ewes were divided into equal groups each containing ten ewes, ewes in first group received intravaginal sponges containing 7.5 mg letrozole for five days followed by intramuscular injection of prostaglandin at time of removal. The second group were treated with standard GPG protocol. Each group were watched for estrus detection by fertile rams and naturally inseminated. Pregnancy diagnosis for inseminated rams were performed at day 15 after insemination. Estrus response were 100% for each group, while onset of estrus were (54.00 ± 0.40 hrs) in letrozole group and (72.64 ± 1.34 hrs) for GPG group. Duration of estrus in letrozole group (25.17 ± 0.24 hrs) were shorter than GPG group (46.52 ± 1.70 hrs). Non return to estrus were 60% in letrozole group compared to 50% GPG group. Pregnancy rate were 60% for letrozole group compared to 50% for GPG group. While number of lamb born/ ewe lambed were higher in letrozole (1.83) group compared to (1.2) for GPG group. Percent of ewe lambed twin were higher in letrozole group (80%) compared to (20%) for GPG group. Letrozole sponges could make differences in estrous synchronization of ewes.