Objectives The AMANHI mortality study aims to use harmonized methods, across eleven sites in eight countries in South Asia and sub- Saharan Africa, to estimate the burden, timing and causes of maternal, fetal and neonatal deaths. It will generate data to help advance the science of cause of death (COD) assignment in developing country settings. Methods This population-based, cohort study is being conducted in the eleven sites where approximately 2 million women of reproductive age are under surveillance to identify and follow-up pregnancies through to six weeks postpartum. All sites are implementing uniform protocols. Verbal autopsies (VAs) are conducted for deaths of pregnant women, newborns or stillbirths to confirm deaths, ascertain timing and collect data on the circumstances around the death to help assign causes. Physicians from the sites are selected and trained to use International Classification of Diseases (ICD) principles to assign CODs from a limited list of programmatically-relevant causes. Where the cause cannot be determined from the VA, physicians assign that option. Every physician who is trained to assign causes of deaths from any of the study countries is tested and accredited before they start COD assignment in AMANHI. Importance of the AMANHI mortality study It is one of the first to generate improved estimates of burden, timing and causes of maternal, fetal and neonatal deaths from empirical data systematically collected in a large prospective cohort of women of reproductive age. AMANHI makes a substantial contribution to global knowledge to inform policies, interventions and investment decisions to reduce these deaths.