Invasive disease due to Haemophilus influenzae typeb (Hib) is common in both HIV infected and un-infected children and immunisation with Hib conjugate vaccines is recommended. However, a few studies done showed that HIV infection blunts antibody response to childhood vaccines. The main objective of this study was to assess the ability of both HIV infected and un-infected Ugandan infants seen at Mulago hospital to mount protective antibody responses and highlight some of the factors that affect response. 159 infants were recruited; 8 were lost to follow up. Of the 151 analyzed, 53 were HIV infected and 98 un-infected. The serum antibody responses were determined by ELISA just before the 3rd dose and a minimum of one month after the dose. 81.6% of the HIV un-infected and 56.6% of the HIV infected achieved protective antibodies after the 3rd dose. 3 doses were better than 2 for both groups. Independent predictors for inadequate antibody response were HIV infection and splenomegally in an HIV infected infant Vitamin A had a potentiating effect on response in infants above 6 months. The study results formed a basis for evaluating the efficacy of the Hib conjugate vaccine in the country.