In The Netherlands, as in many other western countries, pertussis vaccines have been used extensively for more than 40 years. Therefore, it is conceivable that vaccine-induced immunity has affected the evolution of B. pertussis. Consistent with this notion, pertussis has reemerged in The Netherlands, despite high vaccination coverage. Further, a notable change in the population structure of B. pertussis was observed in The Netherlands subsequent to the introduction of vaccination in the 1950s. Finally, we observed antigenic divergence between clinical isolates and vaccine strains, in particular with respect to the surface-associated proteins pertactin and pertussis toxin. Adaptation may have allowed B. pertussis to remain endemic despite widespread vaccination and may have contributed to the reemergence of pertussis in The Netherlands.