The combination vaccine diphtheria and tetanus toxoids and acellular pertussis adsorbed, inactivated poliovirus and Haemophilus b conjugate (tetanus toxoid conjugate) vaccine (DTaP-IPV/Hib), which has been exclusively used in Canada for more than 10 years, is the first DTaP-based vaccine approved in the US that includes both poliovirus and Haemophilus influenzae type b (Hib) antigens. In clinical trials, the combined DTaP-IPV/Hib vaccine induced high immunogenecity against all of the vaccine antigens, including Hib. Administration of the DTaP-IPV/Hib vaccine as a four-dose series in infants provided high levels of seroprotection against diphtheria and tetanus toxoids, poliovirus types 1, 2, and 3, and Hib polyribosyl-ribitol-phosphate capsular polysaccharide conjugated to tetanus toxoid (PRP-T). Immune responses produced after doses 3 and 4 of DTaP-IPV/Hib vaccine were noninferior to those seen with separately administered DTaP, inactivated poliovirus, and Hib vaccines, apart from those against PRP-T in one study. Seroconversion rates for the five pertussis components in DTaP-IPV/Hib vaccine were noninferior to those seen in infants receiving the separately administered vaccines. A serology bridging study showed the noninferiority of four doses of DTaP-IPV/Hib vaccine to three doses of a DTaP vaccine in terms of seroconversion rates for filamentous hemagglutinin and fimbriae 2 and 3, but not pertactin. There were no clinically relevant changes in the immunogenicity of DTaP-IPV/Hib when coadministered with pneumococcal-7-valent-CRM197 vaccine or measles, mumps, and rubella vaccine and varicella zoster vaccine at 15 months. The tolerability profile of DTaP-IPV/Hib vaccine was generally similar to that of separately administered DTaP, IPV, and Hib vaccines.