Abstract---Background: Preterm birth is the leading cause of neonatal mortality and the most common reason for neonatal admission to the hospital. Although the causes of preterm labor are not well understood, the burden of preterm births is clear—preterm births account for approximately 70% of neonatal deaths and 36% of infant deaths as well as 25–50% of cases of long-term neurologic impairment in children. Objective: To compare the effectiveness of the tocolytic action of the standard protocol of Magnesium sulfate versus the combination of Nifedipine and 17 α hydroxyprogesterone injection in the term of acute tocolysis therapy on the perinatal outcome and to abrupt threatened preterm labor between 24 weeks to 33 weeks and 6 days. Patients and methods: A prospective randomized control trial study conducted at Zagazig Maternity Hospital, included 102 pregnant women who presented with threatened preterm labor at the Emergency Department of Zagazig University Maternity Hospital. The participants were divided into two groups, group (1) included 51 caseswho received the standard protocol of Magnesium Sulfate: loading dose 4 g IV; maintenance 2 g/hr for 24 hrs. Group (2) included 51 patients who received nifedipine with the initial dose of 20 mg nifedipine capsules, followed by 20 mg nifedipine retard per 6 hours for the next 48 hours along with 17 α hydroxyprogesterone(prolutone Depot 250 mg Bayer Schering Pharma) IM injection stat dose to be repeated twice weekly for 2 weeks. Both groups were given corticosteroids to enhance fetal lung maturity in the form of Dexamethasone 12 mg for 2 doses 24 hrs apart. Primary outcome: Postponement of birth for at least 48 hrs. after initiation of therapy and secondary outcome: neonatal outcomes and maternal adverse effects. Results: this study showed that there was a statistical difference between both groups in delivery 24 hours (p=0.02) and 72 hours (p=0.03) after admission with less early deliveries among group 2 combined Nifedipine with 17 α hydroxyprogesterone IM injection. There was a higher rate of delivered cases in group 1 magnesium sulfate compared to combined group 2. Regarding maternal outcome, there were statistically significant differences regarding maternal mean blood pressure before and after treatment in group 2 Nifedipine with 17 α hydroxyprogesterone IM injection. Maternal mean blood pressure decreased significantly after treatment than before treatment (P= 0.04). There was a statistically significant difference regarding maternal heart rate before and after treatment in Nifedipine with 17 α hydroxyprogesterone IM injection group 2 (P= 0.04).: Regarding the neonatal outcome, less neonatal respiratory distress was recorded among group 2 the nifedipine with 17 α hydroxyprogesterone (p= 0.02). Conclusion: The addition of 17 α hydroxyprogesterone injection as a uterine quiescent hormone to nifedipine was a very effective novel combination in the treatment of threatened preterm labor and improve neonatal outcomes without compromising maternal safety.