Postpartum haemorrhage remains a leading cause of maternal mortality, despite treatment with conventional methods. In this randomised controlled trial, we compared misoprostol 600 μg (200 μg orally and 400 μg sublingually) with placebo in the treatment of postpartum haemorrhage in addition to routine treatment. One hundred and sixty consenting women who delivered vaginally with measured blood loss ≥500 mL and for whom inadequate uterine contraction was thought to be a possible factor were given either misoprostol or placebo in addition to normal treatment and after routine active management with uterotonics. Blood loss was measured by collection in a special plastic bedpan and side effects of treatment were recorded. Measured average additional blood loss was 325 mL (95% confidence interval [CI] 265 to 384 mL) with misoprostol and 410 mL (95% CI 323 to 498 mL) with placebo. No severe side effects were noted in the use of misoprostol.