Postpartum hemorrhage (PPH) is commonly defined as a blood loss of 500 mL or more within 24 hours after birth and affects about 5% of all women giving birth around the world. Globally, nearly one quarter of all maternal deaths are associated with PPH and, in most low-income countries, it is the main cause of maternal mortality. Improving care during childbirth to prevent PPH is a necessary step towards the achievement of the health targets of the third Sustainable Development Goal (SDG 3), particularly target 3.1: reduce the global maternal mortality ratio to less than 70 per 100 000 live births by 2030. Efforts to prevent and reduce morbidity and mortality due to PPH can help to address the profound inequities in maternal and perinatal health globally. To achieve this, skilled health personnel, health managers, policy-makers and other stakeholders need up-to-date and evidence-informed recommendations to guide clinical policies and practices. In 2019, the Executive Guideline Steering Group (GSG) for World Health Organization (WHO) maternal and perinatal health recommendations prioritized updating of the existing WHO recommendations for advance misoprostol distribution to pregnant women for prevention of PPH in response to the availability of new evidence. The recommendation in this document thus supersedes the previous WHO recommendation for the prevention of PPH as published in the 2012 guideline, WHO recommendations for the prevention and treatment of postpartum hemorrhage.