Background: miscarriage is the process of fetus extraction (embryo) weighting less than 500 mg equivalent to approximately 20 to 22 weeks gestation. Misoprostol is increasingly used for second trimester termination of pregnancy. It is inexpensive, and it is rapidly absorbed by sublingual, vaginal and oral routes. Objectives: This study was carried out for comparing the safety of misoprostol administrated sublingually versus vaginally in the middle of trimester missed miscarriage termination without surgical intervention and with minimum complication. Patients & Methods: The study was carried out in high risk unit of Zagazig university and in Whada Derna teaching hospital during the period from April 2017 to January 2018, 32 pregnant women diagnosed as missed miscarriage were divided to 2 groups, Group A: Received a dose of 200μg of Misoprostol sublingual and Group B: Received a dose of 200μg of Misoprostol vaginally, both each 4 hours up to 6 doses a day. Results: there was a high statistical significant differences the two groups according to the means of induction to miscarriage interval. 15 patients in sublingual group and 7 patients in vaginal group miscarriage during 12 hours after treatment. Conclusion: Sublingual and vaginal administration of 200 microgram of misoprostol each 4 hours up to 6 doses a day is effective in the second trimester termination in missed miscarriage, sublingual administration is the best choice due to its high response, acceptability, less side effects and great effect, sublingual misoprostol can be self- administrated by patients at home thereby decreasing hospital stay and costs.