Objective To test the effect of 800 μg of misoprostol orally on the prevention of manual removal of retained placenta. Design Multicenter, double-blinded, placebo-controlled, randomized trial. Setting One university and one non-university teaching hospital in the Netherlands. Sample 99 women with retained placenta (longer than 60 min after childbirth) in the absence of postpartum hemorrhage. Methods Eligible women were administered either 800 μg of misoprostol or placebo orally. Main outcome measures Number of manual removals of retained placenta and amount of blood loss. Results Manual removal of retained placenta was performed in 50% of the women who received misoprostol and in 55% who received placebo (relative risk 0.91, 95% confidence interval 0.62-1.34). No difference in the amount of blood loss (970 vs. 1120 mL; p = 0.34) was observed between the two groups. Conclusions Administration of 800 μg of oral misoprostol, one hour after childbirth, does not seem to reduce the number of manual removals of retained placentas. The time elapsing results in the delivery of 50% of the retained placentas at the expense of an increased risk of postpartum hemorrhage. © 2013 The Authors Acta Obstetricia et Gynecologica Scandinavica © 2013 Nordic Federation of Societies of Obstetrics and Gynecology.