Background:Since preterm labor and delivery (PTL) is still the leading cause of perinatal morbidity and mortality as well as its long-term consequences, it has a substantial effect on the health of the unborn child. The present study was conducted to compare oral and vaginal natural micronized progesterone in preventing preterm labor. Materials & Methods:90 pregnant women with gestational age between >24 weeks to <36 weeks were divided into 2 groups of 45 each. Group I patients were administered oral micronized progesterone 300 mg and group II were administered vaginal micronized progesterone. APGAR scoreat 5 minutes and birthweight were recorded. Results: Gestational age 24-28 weeks had 13 patients in group I and 15 in group II, 29-32 weeks had 24 in group I and 23 in group II and 32-36 weeks had 8 in group I and 7 in group II. Perinatal outcomes were asymptomatic at birth seen in 35 in group I and 38 in group II, neonatal sepsis in 2 and 1, hypoxemic ischaemic encephalopathy in 3 and 2, meconium aspiration syndrome in 1 and 2, and birth asphyxia in 4 and 2 in group I and II respectively. The difference was significant (P< 0.05). The mean birth weight <2.5 kgs was seen in 11 and 7, 2.5-3 Kgs in 20 and 14 and >3 kgs in 14 and 24 in group I and II respectively. NICU admission was seen in 4in group I and 2 in group II, APGAR score at 1 minute was 7.24 in group I and 8.19 in group II and at 5 minutes was 7.80 in group I and 8.61 in group II. The difference was significant (P< 0.05). Conclusion: Progesterone administered vaginally is thought to be more effective than progesterone taken orally. It is essential in lowering the rate of neonatal NICU admissions, neonatal death, and neonatal morbidity. It also lowers preterm labor.