Background: Preterm birth with a prevalence of about 10% causes 75-95% of prenatal mortality, and one of the effective factors of it is hormonal factors. This study aimed to investigate the effect of oral medroxy progesterone on reducing Preterm labor in women with a history of Preterm labor. Materials and Methods: This double-blinded clinical trial was performed on 214 pregnant women with the history of at least one Preterm labor referred to midwifery clinic of Fatemieh Hospital, Shiraz, Iran, during 2017 to 2018. One hundred and seven women underwent treatment with oral medroxy progesterone (100 mg per day), and 107 individuals were prescribed placebo, and prenatal care was performed routinely. Recent pregnancy course and delivery time were compared in two groups. Data were analyzed by SPSS software version 16. 0. Results: Gestational age with a mean of 30 ± 3. 89 and 36± 2. 11 weeks, respectively in control and intervention groups differed significantly (P <0. 05). The number of referrals to hospital due to Preterm labor, the age of patients at first referral due to Preterm labor, and age of delivery in both groups of receiving progesterone and placebo were significantly different (P <0. 05). Conclusion: Based on the results of the current study using 100 mg oral progesterone per day in weeks 16-36 of pregnancy was effective in reduction of Preterm labor, and caused improved gestational age in mothers.