This article describes and critically appraises clinical trials assessing misoprostol effectiveness in preventing primary postpartum haemorrhage (PPH) in home and community settings in low- and middle-income countries. Of 172 identified studies of misoprostol use in labour only six fulfilled the inclusion criteria. All trials used 600 μg misoprostol in the intervention arm; three assessed misoprostol alongside components of active management of the third-stage labour (AMTSL), two used expectant management of labour and one allowed birth attendants to choose management practice. The three AMTSL studies showed no significant differences in PPH incidence or referral to higher centres and only one study showed significant decrease in severe PPH using misoprostol. One expectant management study and the choice of management by birth attendants study found significant decreases in PPH incidence with misoprostol. All studies showed significantly increased risk of shivering with misoprostol. Studies were biased by use of alternative uterotonics in the control arm, confounding management practices, and subjective assessment and, with one exception, exclusion of high-risk women. PPH incidence fell in both the control and intervention groups in both the landmark papers that informed the World Health Organization (WHO) decision to admit misoprostol to the Essential Medicines List. This suggests factors other than misoprostol use are crucial. Current evidence does not support misoprostol use in home and community settings in low- and middle-income countries for PPH prevention. WHO should rethink its recent decision to include misoprostol on the Essential Medicines List.