Background: Misoprostol is not only economical and effective, but it also has less adverse effects and doesn't require special handling when being used. Patients tolerate this medication well, and it greatly lowers treatment expenses, curettage, and the necessity for surgical intervention. Objective: This work aimed to compare the use of misoprostol and letrozole in combination versus misoprostol alone for medical termination of first-trimester abortions.   Patients and methods: This prospective cohort study included 260 patients. This study was conducted at Menoufia University & El-Sadat Central Hospitals after being approved by the Committee of Medical Ethics. With a GA of age from 6 - ≤ 12 weeks, those who were candidates for abortion were selected and divided into two groups. Group A received 7.5 mg of Letrozole daily (3 tablets of 2.5 mg) for 3 days before taking Misoprostol and group B received Misoprostol only. Results: Successful abortion rate was significantly higher in group A (69.2%) than in group B (57.7%); p=0.0001. There was a significant difference between the two groups regarding time from induction to abortion as group A has a shorter duration from the start of Misoprostol doses to complete abortion than group B with mean 6.2±2.18 vs 9.11±1.92 hours respectively (p value 0.001).Also, therewas a significant difference between both groups as regards doses of misoprostol needed for complete abortion as group A needed lower dose of misoprostol than group B. There was no significant difference between both groups regarding hemoglobin level before and after abortion or side effects of treatment. Conclusion: It could be concluded that using 7.5 mg daily Letrozole for three days, followed by vaginal Misoprostol, leads to a considerably greater rate of complete abortion than misoprostol alone in women with a GA of less than 12 weeks.