BACKGROUND: Prostaglandins have mainly been used for postpartum haemorrhage when other measures fail. Misoprostol, a new and inexpensive prostaglandin E1 analogue, has been suggested as an alternative for routine management of the third stage of labour. OBJECTIVES: The objective of this review was to assess the effects of prophylactic prostaglandin use in the third stage of labour. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register (March, 2002) and Cochrane Controlled Trials Register (Cochrane Library, Issue 2, 2002) were searched. SELECTION CRITERIA: Randomized or quasi-randomized trials comparing a prostaglandin agent with another uterotonic or no prophylactic uterotonic (nothing or placebo) as part of management of the third stage of labour. There were no language preferences. DATA COLLECTION AND ANALYSIS: Eligibility, trial quality and data extraction were done by two reviewers independently. MAIN RESULTS: Seventeen misoprostol and eight intramuscular prostaglandin trials were included. The data comparing oral misoprostol to no uterotonics/placebo are from three trials involving 1700 women and are difficult to interpret because of the heterogeneity between trials. However, the data do not suggest a substantive reduction in the rate of postpartum haemorrhage or other measures of blood loss so far. Oral misoprostol 600 mcg showed clinically and statistically significantly more blood loss >= 1000 mls compared with conventional injectable uterotonics (all trials, 21099 women; relative risk (RR): 1.36, 95% confidence interval (CI): 1.17 to 1.58). Shivering and elevated body temperature (> 38 degrees C) are the main side-effects of misoprostol and are dose related. Compared to oxytocin the RR of any shivering with 600 mcg oral misoprostol is 3.27 (95% CI: 3.01 to 3.56) and temperature > 38C is 6.96 (95% CI: 5.95 to 8.57). Injectable prostaglandins are associated with reduced blood loss in the third stage of labour (weighted mean difference: -70 mls, 95% CI: -73 to -67 mls) when compared to conventional injectable uterotonics but have more side-effects. REVIEWER'S CONCLUSIONS: Neither intramuscular prostaglandins nor misoprostol are preferable to conventional injectable uterotonics as part of the active management of the third stage of labour especially for low-risk women. Future research on prostaglandin use after birth should focus on the treatment of postpartum haemorrhage rather than prevention where they seem to be more promising.