BACKGROUND: Adults infected with HIV have high rates of invasive pneumococcal disease. Introduction of pneumococcal conjugate vaccine for children could affect disease among HIV-infected adults. OBJECTIVE: To compare invasive pneumococcal disease among HIV-infected adults before and after the introduction of a pediatric conjugate vaccine. DESIGN: Active laboratory-based surveillance in an adult population of 10.8 million, including 38,314 living with AIDS. SETTING: 7 Active Bacterial Core surveillance areas in the United States. PATIENTS: All surveillance-area residents 18 to 64 years of age with Streptococcus pneumoniae isolated from a sterile site between 1998 and 2003. MEASUREMENTS: Ratio of the number of cases of invasive pneumococcal disease among HIV-infected adults to the estimated number of adults 18 to 64 years of age living with AIDS; serotype-specific subset analyses; and comparison of periods before and after introduction of conjugate vaccine by using exact tests. RESULTS: Of 8582 cases of invasive pneumococcal disease in adults, 2013 (24%) occurred among persons infected with HIV. Between baseline (1998 to 1999) and 2003, the ratio of invasive pneumococcal disease in HIV-infected adults to the number of adults living with AIDS in the surveillance areas decreased from 1127 to 919 cases per 100 000 AIDS population, a reduction of 19% (P = 0.002). Among HIV-infected adults, the ratio for disease caused by pneumococcal serotypes included in the conjugate vaccine decreased 62% (P < 0.001), although the ratio for disease caused by nonvaccine serotypes increased 44% (P < 0.001). LIMITATIONS: Ratios are proxy measures of incidence rates. The denominator of surveillance-area residents living with HIV infection was not available. CONCLUSIONS: Introduction of the pediatric conjugate vaccine was associated with an overall decrease in invasive pneumococcal disease among HIV-infected adults, despite increased disease caused by nonvaccine serotypes.