The clinical effectiveness of 23-valent pneumococcal vaccine in human immunodeficiency virus (HIV)-infected patients is controversial, because of the low immunological response in these subjects. We studied the clinical response of pneumococcal vaccine and the relative impact of influenza vaccine by administering both pneumococcal and influenza vaccine in a group of 150 HIV patients belonging to all CDC categories. In the group of 90 HIV-infected patients vaccinated against both pneumonia and influenza virus, there was a low incidence of mild influenza (13.3%) and no case of pneumococcal pneumonia. On the contrary, among 60 nonvaccinated HIV patients, 61.6% underwent mild to severe influenza and two developed pneumococcal pneumonia. 23-valent pneumococcal vaccine (PV) seems to be clinically effective in preventing pneumonia in HIV-infected patients, and even more if strengthened by influenza vaccine.