dc.description.abstract Abstract Background The RTS,S/AS01 malaria vaccine candidate recently completed Phase III trials in 11 African sites. Recommendations for its deployment will partly depend on predictions of public health impact in endemic countries. Previous predictions of these used only limited information on underlying vaccine properties and have not considered country-specific contextual data. Methods Each Phase III trial cohort was simulated explicitly using an ensemble of individual-based stochastic models, and many hypothetical vaccine profiles. The true profile was estimated by Bayesian fitting of these models to the site- and time-specific incidence of clinical malaria in both trial arms over 18 months of follow-up. Health impacts of implementation via two vaccine schedules in 43 endemic sub-Saharan African countries, using country-specific prevalence, access to care, immunisation coverage and demography data, were predicted via weighted averaging over many simulations. Results The efficacy against infection of three doses of vaccine was initially approximately 65 % (when immunising 6–12 week old infants) and 80 % (children 5–17 months old), with a 1 year half-life (exponential decay). Either schedule will avert substantial disease, but predicted impact strongly depends on the decay rate of vaccine effects and average transmission intensity. Conclusions For the first time Phase III site- and time-specific data were available to estimate both the underlying profile of RTS,S/AS01 and likely country-specific health impacts. Initial efficacy will probably be high, but decay rapidly. Adding RTS,S to existing control programs, assuming continuation of current levels of malaria exposure and of health system performance, will potentially avert 100–580 malaria deaths and 45,000 to 80,000 clinical episodes per 100,000 fully vaccinated children over an initial 10-year phase.