Invasive disease from Streptococcus pneumoniae (pneumococcus) is a major cause of illness and death in the United States, with an estimated 43,500 cases and 5,000 deaths among persons of all ages in 2009. This report provides updated recommendations from the Advisory Committee on Immunization Practices (ACIP) for prevention of invasive pneumococcal disease (IPD) (i.e., bacteremia, meningitis, or infection of other normally sterile sites) through use of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) among all adults aged >or=65 years and those adults aged 19-64 years with underlying medical conditions that put them at greater risk for serious pneumococcal infection. The new recommendations include the following changes from 1997 ACIP recommendations: 1) the indications for which PPSV23 vaccination is recommended now include smoking and asthma, and 2) routine use of PPSV23 is no longer recommended for Alaska Natives or American Indians aged <65 years unless they have medical or other indications for PPSV23. ACIP recommendations for revaccination with PPSV23 among the adult patient groups at greatest risk for IPD (i.e., persons with functional or anatomic asplenia and persons with immunocompromising conditions) remain unchanged. ACIP recommendations for prevention of pneumococcal disease among infants and youths aged <or=18 years using the 13-valent pneumococcal conjugate vaccine (PCV13) and PPSV23 are published separately.