BackgroundMeta-analyses of postpartum blood loss and the effect of uterotonics are biased by visually estimated blood loss.ObjectivesTo conduct a systematic review of measured postpartum blood loss with and without prophylactic uterotonics for prevention of postpartum haemorrhage (PPH).Search strategyWe searched Medline and PubMed terms (labour stage, third) AND (ergonovine, ergonovine tartrate, methylergonovine, oxytocin, oxytocics or misoprostol) AND (postpartum haemorrhage or haemorrhage) and Cochrane reviews without any language restriction.Selection criteriaRefereed publications in the period 1988–2007 reporting mean postpartum blood loss, PPH (≥500 ml) or severe PPH (≥1000 ml) following vaginal births.Data collection and analysisRaw data were abstracted into Excel by one author and then reviewed by a co-author. Data were transferred to SPSS 17.0, and copied into RevMan 5.0 to perform random effects meta-analysis.Main resultsThe distribution of average blood loss (29 studies) is similar with any prophylactic uterotonic, and is lower than without prophylaxis. Compared with no uterotonic, oxytocin and misoprostol have lower PPH (OR 0.43, 95% CI 0.23–0.81; OR 0.73, 95% CI 0.50–1.08, respectively) and severe PPH rates (OR 0.61, 95% CI 0.29–1.29; OR 0.74, 95% CI 0.52–1.04, respectively). Oxytocin has lower PPH (OR 0.65, 95% CI 0.60–0.70) and severe PPH (OR 0.71, 95% CI 0.56–0.91) rates than misoprostol, but not in developing countries.ConclusionOxytocin is superior to misoprostol in hospitals. Misoprostol substantially lowers PPH and severe PPH. A sound assessment of the relative merits of the two drugs is needed in rural areas of developing countries, where most PPH deaths occur.