The frequency of meningitis due to penicillin-resistant Streptococcus pneumoniae (PRP) has increased in recent years, making treatment failure more likely. It is currently expected that pneumococcal conjugate vaccines might curb this trend. We investigated this issue using a mathematical model applied to the current prevalence of resistance and antibiotic exposure in the United States and in France. Our main finding was that the level of antibiotic exposure may limit the effect of the vaccine. In relatively low antibiotic exposure environments such as the United States, large-scale vaccination prevents a large part of PRP meningitis cases, whereas in high antibiotic-exposure environments such as France, vaccination alone does not lead to a substantial reduction in PRP meningitis incidence. Our results suggest that antibiotic exposure reduction will remain of primary importance for the control of PRP meningitis despite wide scale use of pneumococcal conjugate vaccines.