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The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced for routine administration to infants and children in 2010 in the United States. We have monitored clinical and microbiologic features of invasive pneumococcal infections among children before and after PCV13 use.Infants and children cared for at 8 children hospitals in the United States with culture-proven invasive infections caused by S. pneumoniae were identified in an ongoing prospective surveillance study. Demographic and clinical data were recorded on a standard case report form. Serotype and antimicrobial susceptibilities of isolates were determined.Since routine PCV13 immunization in 2010, invasive pneumococcal infections decreased 42% overall and 53% for children <24 months of age in 2011 compared with the average number of cases for 2007 to 2009. PCV13 serotype isolates decreased 57% during these same time periods; 19A, 7F and 3 decreased by 58%, 54% and 68%, respectively. The number of infections caused by serotypes 1 and 6C also decreased in 2011. The most common non-PCV13 serotypes encountered in 2010 and 2011 combined were 33F, 22F, 12, 15B, 15C, 23A and 11. Bacteremia, pneumonia and mastoiditis cases decreased more than meningitis cases.After the introduction of PCV13, invasive pneumococcal infections decreased among 8 children hospitals compared with the 3 years before PCV13 use. Slight increases in some non-PCV13 serotype isolates were noted in 2011. Continued surveillance is necessary to determine the effectiveness of PCV13 including herd protection as well as any emerging invasive serotypes.