Invasive pneumococcal disease (PD) occurs frequently among HIV-infected patients, but it is unclear whether its manifestations and outcome are different compared to those observed among patients without HIV-1 infection. Because the immune reconstitution that accompanies antiretroviral therapy may change some of these features and because most cases of HIV- 1 infection occur in resource-poor settings of the world where access to antiretroviral agents is limited, we compared PD among patients with and without HIV-1 infection in a North American population before the introduction of highly active antiretroviral therapy (HAART). The records of all pneumococcal cultures processed at this medical center over a period of 20 months were used to identify patients with invasive PD. Hospital records were reviewed for 103 of these patients (52 with and 51 without HIV-1 infection) and demographic, clinical, laboratory, radiographic, and microbiologic information was abstracted and subsequently analyzed. Despite similarities in presenting signs and symptoms, we found a higher incidence of bacteremia but a more favorable outcome with less frequent requirements for intubation and admission to intensive care units and better survival among individuals with HIV infection. Factors such as less advanced age, the presence of fewer comorbid conditions, or a less florid inflammatory response among HIV-infected individuals may account for differences in outcome of invasive PD.