The first Hib vaccine licensed was a pure polysaccharide vaccine, first marketed in the US in 1985. Similar to other polysaccharide vaccines, immune response to the vaccine was highly age dependent. Children under 18 months of age did not produce a positive response for this vaccine. As a result, the age group with the highest incidence of Hib disease was unprotected, limiting the usefulness of the vaccine. The vaccine was withdrawn from the market in 1988.

The shortcomings of the polysaccharide vaccine lead to the production of the Hib polysaccharide-protein conjugate vaccine. Attaching Hib polysaccharide to a protein carrier greatly increased the ability of the immune system of young children to recognize the polysaccharide and develop immunity. There are currently three types of conjugate vaccine utilizing different proteins in the conjugation process, all of which are highly effective: tetanospasmin(also called tetanus toxin), mutant diphtheria protein, and meningococcal group B outer membrane protein.

Multiple combinations of Hib and other vaccines have been licensed in the United States, reducing the number of shots necessary to vaccinate a child. Hib vaccine combined with diphtheria-tetanus-pertussis-polio vaccines and Hepatitis B vaccines are available in the US. The World Health Organization (WHO) has certified several Hib vaccine combinations, including a pentavalent diphtheria-pertussis-tetanus-hepatitis B-Hib, for use in developing countries.

Hib conjugate vaccines have been shown to be universally effective against all manifestations of Hib disease, with a clinical efficacy among fully vaccinated children estimated to be between 95-100%. The vaccine has also been shown to be immunogenic in patients who are at high risk of invasive disease. Hib vaccine is not effective against non-type B Haemophilus influenzae. However, non-type B disease is rare in comparison to pre-vaccine Haemophilus influenzae type B disease.

Clinical trials and ongoing surveillance have shown Hib vaccine to be safe. Adverse reactions to the vaccine are generally mild. The most common reactions are transient redness, swelling, or pain at the site of injection, occurring in 5-30% of vaccine recipients. More severe reactions are extremely rare.[quantify]

Prior to introduction of the conjugate vaccine, Hib was a leading cause of childhood meningitis, pneumonia, and inflammation of the epiglottis in the United States, causing an estimated 20,000 cases a year in the early 1980s, mostly in children under 5 years old. Since routine vaccination began, the incidence of Hib disease has declined by greater than 99%, effectively eliminating Hib as a public health problem. Similar reductions in disease occurred after introduction of the vaccine in Western Europe and developing countries.

Although Hib vaccine is given to children, Hib infections have also decreased in adults. This decrease occurred because of herd immunity; children infected with Hib carry the bacteria in their nasal passages while clearing the infection. These Hib carrying children would regularly infect adults. Vaccinating children eliminated the source of the bacteria, reducing the rate of Hib in adults.

The CDC and WHO currently recommend that all infants should be vaccinated using a polysaccharide-protein conjugate Hib vaccine, starting after the age of 6 weeks. Specific immunization schedule depends on choice of vaccine and local recommendations.

Introduction of Hib vaccine in developing countries lagged behind developed countries for several reasons. The expense of the vaccine was large in comparison to the standard EPI vaccines. Poor disease surveillance systems and inadequate hospital laboratories failed to detect the disease, leading many experts to believe that Hib did not exist in their countries. Finally, health systems in many countries were struggling with the current vaccines they were trying to deliver.

To remedy these issues the GAVI Alliance took active interest in the vaccine. GAVI offers substantial subsidization of Hib vaccine for countries who are interested in using the vaccine, as well as financial support for vaccine systems and safe injections. Additionally, GAVI created the Hib Initiative to catalyze uptake of the vaccine. The Hib Initiative uses a combination of collecting and disseminating existing data, research, and advocacy to assist countries in the making a decision abut using the Hib vaccine. Currently[update], 61 out of 72 low-income countries are planning on introducing the vaccine by the end of 2009.