Background and objective: The objective of this work is to match the security and effectiveness of two treatment modalities (Misoprostol versus Letrozol with Misoprostol) in medical treatment of 1st trimesteric missed miscarriages. Methods: This is an interventional randomized case-control investigation that was performed at the outpatient antenatal care clinic of Luxor General Hospital during the period from February to December 2017. The study included a number of 200 cases who have been randomly classified to 2 equal groups: Group-I "Misoprostol" which included 100 cases received 800-mg of misoprostol vaginally at once of diagnosis and group-II "Letrozol + Misoprostol" which included 100 cases received 10-mg letrozol 2 times a day for 3-days as pretreatment then 800-mg of vaginal misoprostol. Results: Misoprostol alone group (group-I) has a significantly high duration of vaginal bleeding after the 1st Misoprostol dose and time passed after 1st misoprostol dose till the 1st passage of POC in comparison with group-II, (P-value Conclusion: The results revealed that a 3-days course of letrozole (10-mg per day) trailed by misoprostol vaginally (800-mg) was accompanied with a significantly high full abortions rate in women with first-trimester miscarriage compared to misoprostol alone (81.0% vs. 54.0%) without increasing side effects.