Since mid-2011, a substantial rise in pertussis cases has been reported in the state of Washington. In response to this increase, the Washington State Secretary of Health declared a pertussis epidemic on April 3, 2012. By June 16, the reported number of cases in Washington in 2012 had reached 2,520 (37.5 cases per 100,000 residents), a 1,300% increase compared with the same period in 2011 and the highest number of cases reported in any year since 1942. To assess clinical, epidemiologic, and laboratory factors associated with this increase, all pertussis cases reported during January 1-June 16, 2012, were reviewed. Consistent with national trends, high rates of pertussis were observed among infants aged <1 year and children aged 10 years. However, the incidence in adolescents aged 13-14 years also was increased, despite high rates of vaccination with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine, suggesting early waning of immunity. The focus of prevention and control efforts is the protection of infants and others at greatest risk for severe disease and improving vaccination coverage in adolescents and adults, especially those who are pregnant. Pertussis vaccination remains the single most effective strategy for prevention of infection.