Background: Preterm labor (PTL) is the leading cause of perinatal and neonatal morbidity and mortality and strongly related to the developmental and neurological disabilities later in life. Objective: To compare between calcium channel blocker and progesterone in the prevention of Preterm Labor in patients with history of recurrent spontaneous preterm labor. Patients and Methods: A comparative clinical study was done at Al-Hussein Hospital on one hundred pregnant women with history of previous spontaneous preterm labors were selected in this study, and randomly arranged into two groups: calcium channel blocker group (A), and progesterone group (B). Results: There was no statistically significant difference between all groups as regards age, parity and number of previous preterm labors, There was a statistically significant difference between the progesterone group and the calcium group as regards GA at delivery, with higher percentage of lower GA at delivery among the progesterone group (35.61 weeks) compared to the calcium group (37.11 weeks), There was a statistically significant difference between the progesterone group and the calcium group as regards mean values of birth weight with higher percentage of lower birth weight among the progesterone group (2.37 kg) compared to the calcium group (2.93 kg), There was a statistically significant difference between the progesterone group and the calcium group as regards mean values of five minutes APGAR Score with higher percentage of lower five minutes APGAR Score among the progesterone group (7.66) compared to the calcium group (8.57), There was no statistically significant difference between all groups as regards the mode of delivery. There was a statistically significant difference between the progesterone group and the calcium group as regards NICU admission with higher percentage of NICU admission among the progesterone group (40%) compared to the calcium group (17.1%), There was a statistically significant difference in different studied groups before and after progesterone administration as regards mean values of serum progesterone, There was a statistically significant difference in different studied groups before and after progesterone administration as regards mean values of serum calcium. Conclusion: The use of calcium channel blocker and progesterone reduced the rate of preterm labor, prolonged gestational age at delivery, reduced the frequency of uterine contractions, and improved the symptoms of preterm labor in women with history of recurrent spontaneous preterm labors. Calcium channel blocker was more superior on progesterone as regards prevention of recurrent preterm labor.