Changes in invasive pneumococcal disease (IPD) incidence were evaluated after 7 years of 7-valent pneumococcal conjugate vaccine (PCV7) use in US children. Laboratory-confirmed IPD cases were identified during 1998-2007 by 8 active population-based surveillance sites. We compared overall, age group-specific, syndrome-specific, and serotype group-specific IPD incidence in 2007 with that in 1998-1999 (before PCV7) and assessed potential serotype coverage of new conjugate vaccine formulations. Overall and PCV7-type IPD incidence declined by 45% (from 24.4 to 13.5 cases per 100,000 population) and 94% (from 15.5 to 1.0 cases per 100,000 population), respectively (P< .01 all age groups). The incidence of IPD caused by serotype 19A and other non-PCV7 types increased from 0.8 to 2.7 cases per 100,000 population and from 6.1 to 7.9 cases per 100,000 population, respectively (P< .01 for all age groups). The rates of meningitis and invasive pneumonia caused by non-PCV7 types increased for all age groups (P< .05), whereas the rates of primary bacteremia caused by these serotypes did not change. In 2006-2007, PCV7 types caused 2% of IPD cases, and the 6 additional serotypes included in an investigational 13-valent conjugate vaccine caused 63% of IPD cases among children <5 years-old. Dramatic reductions in IPD after PCV7 introduction in the United States remain evident 7 years later. IPD rates caused by serotype 19A and other non-PCV7 types have increased but remain low relative to decreases in PCV7-type IPD.