Reported common reactions to Hib vaccine include fever and pain and swelling at injection site. Rash, hives, irritability, restless sleep, prolonged crying; diarrhea, vomiting, loss of appetite, convulsions, collapse/shock, and Guillain-Barre syndrome have also been reported. Some of the studies used to evaluate the reactivity of Hib vaccine were complicated by the fact that Hib vaccine was given simultaneously with DPT an OPV vaccine. When a reaction occurred, it was difficult to determine which vaccines were responsible for the reaction.

In 1994, the Institute of Medicine concluded that there is compelling scientific evidence that vaccination with earlier versions of the Hib vaccine resulted in early onset of Hib disease in children over 18 months of age. Apparently, the early Hib vaccines caused children, who had been recently vaccinated, to be immune suppressed for at least 7 days after vaccination.

The conjugate Hib vaccines now being used are thought to be more quickly effective, leaving children less vulnerable to Hib disease shortly after vaccination. However, the IOM report stated that "Because immunization with Hib vaccines may lead to a transient decrease in protective antibody levels, unimmunized children at increased risk of colonization (household or day-care contact with individuals with recent cases of Hib infection) may require special [protective] measures." One Hib vaccine manufacturer states, "There have been rare reports to the Vaccine Adverse Events Reporting System (VAERS) of Hib disease following full primary immunization."

Because either no studies or too few studies have ever been conducted to investigate Hib vaccine reactions, the IOM could not make a determination about whether Hib vaccine causes transverse myelitis, Guillain-Barre syndrome, thrombocytopenia, anaphylaxis and sudden infant death syndrome.

A manufacturer of HIB vaccine states in the product insert that the vaccine "has not been evaluated for its carcinogenic, mutagenic potential or impairment of fertility" and "it is also not known whether [the vaccine] can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity."

In 1995, out of 74 Hib disease cases where age and vaccination status were known, 41 or 55 percent had received at least one Hib shot; 22 were appropriately vaccinated for their age; and 18 had completed the primary series.