Despite the concern of replacement disease, notably by serotype 19A after 7-valent conjugate vaccine (PCV7) use, serotype 19A was increasingly recognized in Korean children before the introduction of PCV7. To understand the dynamics of serogroup 19 prevalence from 1991-2006, we serotyped 538 pediatric pneumococcal isolates. Serogroup 19 isolates (n = 126) were characterized by antimicrobial drug susceptibility, presence of mefA/ermB, and multilocus sequence typing. Overall, the proportion of serotype 19A isolates increased but serotype 19F decreased. Among children <5 years of age, the proportion of serotype 19A isolates in invasive pneumococcal disease increased from 0% in 1991-1994 to 8%-10% in 1995-2000, reached 26% in 2001-2003, and remained at 20% in 2004-2006 when vaccine coverage did not exceed 25% (p = 0.005 for trend). This study demonstrates that the expansion of multidrug-resistant ST320 was responsible for the increase in serotype 19A before PCV7 use.