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Objective To study the effectiveness of the Haemophilus influenzae type b (Hib) vaccination program in Uganda. Methods Case–control study of Hib vaccine effectiveness against Hib meningitis. Cases were children hospitalized with Hib meningitis confirmed by culture and/or latex agglutination. Cases were identified retrospectively from July 2002 to July 2004, and prospectively from July 2004 to July 2005. Each case-patient was matched by age to three neighbourhood and three hospital controls; all children were eligible to receive Hib vaccine through the routine schedule. Vaccine effectiveness was evaluated by conditional logistic regression, controlling for confounding variables. Results We enrolled 41 cases; their median age was 6 months. Only six (15%) cases, all HIV-negative, had received ≥2 doses of Hib vaccine, compared with 64% of neighbourhood controls and 70% of hospital controls. Controlling for maternal education, the only variable which remained in the multivariable model, vaccine effectiveness for two or three doses vs. no dose was 99% [95% confidence intervals (CI) 92–100%] and 96% (95% CI 80–100%) when cases were compared with neighbourhood and hospital controls, respectively. Conclusion In Uganda, Hib vaccine was highly effective in the context of the routine immunization schedule. Sustained routine use of Hib vaccine will contribute to the prevention of childhood morbidity and mortality. [ABSTRACT FROM AUTHOR]