This retrospective cohort study compares organisms responsible for septic arthritis and osteomyelitis before and after Haemophilus influenzae type b vaccination. Before vaccination, Haemophilus influenzae type b was responsible for 5% of culture positive osteomyelitis and 41% of culture positive septic arthritis. Since the administration of the conjugated vaccine PRP-T began in 1992, no case of osteomyelitis or septic arthritis has been caused by Haemophilus influenzae type b (p < 0.005, t test). Vaccination has succeeded in eliminating Haemophilus influenzae type b as an infective agent in hematogenous septic arthritis and osteomyelitis. Current empirical antibiotic therapy for hematogenous septic arthritis and osteomyelitis need only cover gram-positive agents in vaccinated infants and children of all age groups.