We predict the effects of introduction of a pre-erythrocytic vaccine against Plasmodium falciparum into a malaria-endemic population in Africa. We use a stochastic simulation model that includes components of transmission, parasitology, and clinical epidemiology of malaria and was validated using the results of field trials of the RTS,S/AS02A vaccine. The results suggest that vaccines with efficacy similar to that of RTS,S/AS02A have a substantial impact on malaria morbidity and mortality during the first decade after their introduction, but have negligible effects on malaria transmission at levels of endemicity typical for sub-Saharan Africa. The main benefits result from prevention of morbidity and mortality in the first years of life. Vaccines with very short half-life or low efficacy may have little overall effect on incidence of severe malaria. A similar approach can be used to make predictions for other strategies for deployment of the vaccine and to other types of malaria vaccines and interventions.