BACKGROUND: In 2012 England and Wales experienced a resurgence of pertussis and an increase in infant deaths. This occurred 8 years after acellular pertussis (aP) vaccine replaced whole cell (wP) primary vaccine despite continued high coverage for the primary series and pre-school aP booster. We developed a mathematical model to describe pertussis transmission dynamics in England and Wales since the 1950s and used it to investigate the cause of the resurgence and the potential impact of additional vaccination strategies. METHODS: An age-structured, compartmental, deterministic model of the pertussis transmission dynamics was fitted to 60 continuous years of age-stratified pertussis notification data in England and Wales. The model incorporated vaccine-induced and natural immunity and differentiated between vaccine-induced protection against clinical disease and infection. RESULTS: The degree of protection of wP vaccine against infection was estimated to be higher than that of aP vaccine. Furthermore, the duration of protection for natural and wP-induced immunity was likely to be at least 15 years, but for aP vaccine it could be as low as 5 years. Model results indicated that the likely cause of the resurgence was the replacement of wP by less efficacious aP vaccine and that an elevated level of pertussis would continue. The collapse in wP vaccine coverage in the 1970s and resultant outbreaks in the late 1970s and early 1980s could not explain the resurgence. Addition of an adolescent or toddler booster was predicted to have little impact on the disease in infants. CONCLUSIONS: Our findings support the recent recommendation by the World Health Organisation that countries currently using wP vaccine for primary immunisation should not change to aP vaccine unless additional strategies to control infant disease such as maternal immunisation can be assured. Improved pertussis vaccines that provide better protection against infection are needed.