BACKGROUND: Using misoprostol to prevent postpartum haemorrhage (PPH) in home-birth settings remains controversial. OBJECTIVES: To review the safety and effectiveness of oral misoprostol in preventing PPH in home-birth settings. SEARCH STRATEGY: The Cochrane Library, PubMed, and POPLINE were searched for articles published until 31 March 2012. SELECTION CRITERIA: Studies, conducted in low-resource countries, comparing oral misoprostol with a placebo or no treatment in a home-birth setting. Studies of misoprostol administered by other routes were excluded. DATA COLLECTION AND ANALYSIS: Data were extracted by two reviewers and independently checked for accuracy by a third. The quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Data were sythesised and meta-analysis was performed where appropriate. MAIN RESULTS: Ten papers describing two randomised and four non randomised trials. Administration of misoprostol was associated with a significant reduction in the incidence of PPH (RR 0.58, 95% CI 0.38-0.87), additional uterotonics (RR 0.34, 95% CI 0.16-0.73), and referral for PPH (RR 0.49, 95% CI 0.37-0.66). None of the studies was large enough to detect a difference in maternal mortality, and none reported neonatal mortality. Shivering and pyrexia were the most common side effects. AUTHOR'S CONCLUSIONS: The finding that the distribution of oral misoprostol through frontline health workers is effective in reducing the incidence of PPH could be a significant step forwards in reducing maternal deaths in low-resource countries. However, given the limited number of high-quality studies in this review, further randomised controlled trials are required to confirm the association, particularly in different implementation settings. Adverse effects have not been systematically captured, and there has been limited consideration of the potential for inappropriate or inadvertent use of misoprostol. Further evidence is needed to inform the development of implementation and safety guidelines on the routine availability of misoprostol.