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Objective: To assess the effects of prophylactic misoprostol use in the third stage of labor compared with injectable uterotonics or placebo or no treatment., Data Sources: The Cochrane Pregnancy and Childbirth Group trials register; the Cochrane Library, including databases such as the database of systematic reviews and the Cochrane Controlled Trials Register; and MEDLINE were searched. Researchers in the field were also contacted. The date of the latest search was March 1, 2002., Methods of Study Selection: Randomized trials comparing misoprostol with injectable oxytocin or oxytocin-ergot preparations to prevent postpartum hemorrhage or placebo/no treatment as active management of the third stage of labor were eligible for inclusion. Eligibility and trial quality were assessed following selected criteria. Data were extracted and analyzed using RevMan software., Tabulation, Integration, and Results: Sixteen randomized trials with a total of 28,138 women were considered. Data were available for 27,498 women. Oral misoprostol (600 microg) is less effective than injectable uterotonics in reducing blood loss at least 1000 mL (relative risk [RR] 1.36, 95% confidence interval [CI] 1.17, 1.58) and increases the use of additional uterotonics. Shivering and pyrexia (temperature greater than 38C) are the main side effects of misoprostol and are dose related. Compared with injectable uterotonics, the RR of "any shivering" with misoprostol (600 microg) is 3.27 (95% CI 3.01, 3.56) and pyrexia is 6.96 (95% CI 5.65, 8.57). The RR of blood loss of 500 mL or more is 1.11 (95% CI 0.87, 1.43) and the RR of use of additional uterotonics is 1.80 (1.13, 2.85) in the three trials (1441 women) comparing rectal misoprostol (400 microg) with injectable uterotonics., Conclusion: Injectable oxytocin or oxytocin-ergot preparations are more effective than misoprostol as part of the active management of the third stage of labor.