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Background: Prematurity is the leading cause of neonatal morbidity and mortality. Although perinatal care advanced in the last few decades, preterm labor did not decrease but even is increasing and creating a great social and economic problem. Objective: To test the effectiveness of progesterone vaginal suppository in prevention of preterm labor in patients with previous history of preterm labor. Patients and Methods: This was a randomized , prospective, single blind study after approval of the medical ethical committee at Al-Azhar university Hospitals, Department of Obstetrics and Gynecology, and after patients giving written consents, during the period from February 2020 to October 2020 . We enrolled 168 women for the study at high risk for preterm labor who were randomly divided into two groups (progesterone group and placebo group). Two hundred mg of vaginal progesterone pessary or placebo were used by the patient from 24 to 36 weeks of gestation. Uterine contractions were recorded by external tocodynamometer every other week from 28 to 36 weeks of gestations. Results: There was a statistically significant reduction in the incidence of preterm delivery between the two groups from 38.5% in placebo group, compared with 21% in progesterone group. There was also a statistically significant reduction in the incidence of early preterm delivery ( |