Abstract Background: Newborn respiratory distress occurs in about 7% of deliveries. The most common etiology of respiratory distress in newborns is TTN, which occurs in about five or six per 1,000 births. Aim of Study: To evaluate the effect of Misoprostol (Prostaglandin E1) when given to women undergoing caesarean section on decreasing the incidence of the neonatal respiratory distress assessed by neonatal catecholamines. Patients and Methods: This study a parallel, randomized placebo controlled trial, comparing the use of Misoprostol (Prostaglandin E1) use in the form of Misoprostol E1 vaginal tablets with non-medicated similar vaginal tablet (placebo) to decrease the neonatal respiratory distress specially (TTN). We take 300 cases randomly distributed into two groups: The first group (group I) was included 150 women, were given Misoprostol (prostaglandin E1), and the second one (group II) was consisted of 150 women, were given placebo. Results: There was no significant difference between the study and the control groups regarding neonatal condition. Respiratory rate was significantly lower among study group than among control group. There was no significant difference between both groups as regard tachypnea, retractions and TTN. There was no complication to PE occurred in our current study as uterine hyperstimulation, uterine rupture or meconuim staining of liquor. Conclusion: Administration of PG1 should be not more than one hour before delivery and under complete medical observation cover. We suggest involving only elective cases between 28 weeks to less than 39 weeks, any case with medical disorders or risk should be excluded.