Background: Preterm birth (PTB) is a complex condition leading to neonatal morbidity and mortality. It is the second leading cause of mortality before the age of 5 years. The risk of morbidity also extends to later life. Many efforts have been done to prevent Preterm birth in order to decrease future complications. Dehydrogestrone has a good safety and tolerability profile. It is structurally and pharmacologically similar to natural progesterone and has good oral bioavailability with few side effects. Dehydrogestrone has no androgenic effects on the fetus, and does not inhibit the formation of progesterone in the placenta. Objective: To evaluate the intramuscular 17 alpha-hydroxyprogesterone, natural progesterone suppositories, and dehydrogestrone tablets in preventing preterm labor. Patients and Methods: This was a comparative study, involving 300 pregnant women attended outpatient clinic of Al-Hussein University Hospital, and diagnosed at risk of preterm labor. Those patients were allocated into three equal groups: Group (A) received vaginal Progesterone suppositories, Group (B) received intramuscular 17 alpha hydroxyprogesterone Injections, and Group (C) received oral dehydrogestrone tablets, during the period from January 2020 to December 2021. Results: There was no significant difference between the groups in term of preterm labor, short cervix, and mid-trimestric miscarriage. There was a significant difference regarding middle cerebral artery resistance index before and after treatment as it decreased in Group (C) than Group (A) and Group (B). Regarding middle cerebral artery pulsatility index also there was a decrease after treatment in Group (B) than Group (A) and (C). There was a difference regarding umbilical artery pulsatility index after treatment as it increased in Group (A), Group (B) and Group (C). Moreover, there was a significant increase in umbilical artery resistance index in Group (C) than Group (A) and (B). There was no significant difference between the three groups in term of preterm delivery.      There was no significant difference between the three groups in term of neonatal complications. Conclusion: Vaginal progesterone suppositories, intramuscular 17-alpha hydroxyprogesterone injections, and oral dehydrogestrone tablets have the same effect on the rate of PTB in asymptomatic women with a sonographically short cervix, and there was no significant difference between the effects of three drugs on the cervical length (CL) changes over time.