The emergence and subsequent dominance of MLVA 27 and the MLST alleles prn2 and ptxP3 (in that order, temporally) in the United States occurred during the period with the highest diversity, period 3.The timing and order of these transitions are consistent with global trends (16) in which the emergence of nonvaccine-type alleles for ptxS1 and prn appeared 15–30 years after the introduction of pertussis vaccines. The gene discussed is CIAO3; the disease is pertussis.