Background: Preterm delivery (PTD) is defined as delivery before 37 weeks of gestation, and it raises the risk of perinatal mortality. Additionally, vaginal progesterone effectively improves newborn outcomes and lowers the chance of preterm delivery in these patients. This study aimed to evaluate the role of vaginal progesterone administration in the prevention of preterm labour in patient with history of spontaneous preterm delivery. Patients and methods: A prospective cohort study was carried out at Department of Obstetrics and Gynecology, Faculty of Medicine, Zagazig University Hospital outpatient clinic, and ultrasound fetal medicine unit for a period of 6 months. included 50 patients with a history of spontaneous PTD and divided them into two groups. Patients in the first group were given progesterone (prontogest) 400mg vaginal suppository daily at night and whose cervical length was ≤25mm. The second group of women were not given any drugs with cervical length >25mm. Results: Mean cervical length at 18–24w of gestation showed significant difference between both groups, with a mean cervical length of 21.3±2.9mm for progesterone group and 29.9±3.3mm for control group, and the rate of PTL was significantly less in progesterone group (48%), compared to control group (80%). Neonatal deaths (2%, 16%) were significantly better in the progesterone group than in the control group. Conclusion: Vaginal progesterone is efficacious and safe for reducing the risk of preterm birth and neonatal morbidity and mortality in women with a singleton gestation with a mid-trimester sonographic short cervix.