Diphtheria-tetanus-acellular pertussis vaccines have been licensed in the United States since 1991. Compared with the whole cell pertussis component diphtheria-tetanus-pertussis vaccine, the diphtheria-tetanus-acellular pertussis vaccines were found in reactogenicity and immunogenicity studies to be immunogenic with respect to their specific antigen content and to be associated with less severe and less frequent adverse reactions. A case definition of pertussis was developed by the World Health Organization for use in vaccine efficacy trials, but this definition eliminates some laboratory-confirmed cases from efficacy calculations. Because these cases are more common in vaccinees than in controls, vaccine efficacy appears better than it truly is whereas less effective vaccines seem comparable with their more effective counterparts. In addition observer bias may contribute to the appearance of enhanced efficacy of the less effective vaccines, which tend to prevent typical but not mild disease. When analyzing efficacy based on prevention of laboratory-confirmed pertussis with cough > or = 7 days, single component pertussis toxin (PT) toxoid vaccines were found to be less effective than two-component PT toxoid/filamentous hemagglutinin vaccines, and three- or four-component vaccines containing pertactin in addition to PT toxoid and filamentous hemagglutinin were more effective than either the single-component or two-component vaccines.