This paper describes the influence of vaccination against Haemophilus influenzae type b on epidemiology of the diseases this pathogen causes in Croatia. The data were obtained by examining the available data from the Epidemiological Service of the Croatian Institute for Public Health. In the period prior to the introduction of H. influenzae type b vaccine in Croatia, H. influenzae type b was the leading cause of bacterial meningitis in children aged 3 months to 3 years. The disease can result in grave consequences and permanent disability and, therefore, it has been a public health problem, not only in Croatia, but also in the world. By introducing a vaccine against H. influenzae type b in the mandatory vaccination program in 2002, significant changes in the epidemiology of invasive diseases caused by this pathogen have occurred. Reduction in morbidity was observed shortly after the vaccine was introduced, and the overall morbidity in children younger than 5 years has decreased by more than 99% to date. Given the continuous reduction in the number of vaccinated children in the last few years, such an excellent outcome in the future is questionable. In order to keep the morbidity below 1%, at least 95% of children scheduled for vaccination must be vaccinated. In the elderly population, there is also a marked reduction in the incidence of the invasive disease, and the average age of patients affected by this disease is increasing. Vaccination has led to a change in the strains of H. influenzae which are responsible for the clinical presentation. Nowdays, the non-viable strains of H. influenzae have the main role in causing the invasive disease. The microbiological image has also changed. Increased resistance to ampicillin in isolates was observed, with 24% resistent isolates in 2016. This paper has only reaffirmed the fact that vaccination is effective and, as a simple and cost-effective method, it can effectively prevent diseases that would otherwise be a great burden to the Croatian health system.