ABSTRACT To investigate the characteristics of main Streptococcus pneumoniae clones of serotype 6D (ST282 and ST3171) in South Korea, antimicrobial susceptibility testing was performed, and 11 genes around the cps locus were sequenced on ST282 ^6D , ST3171 ^6D , and ST81 ^6A isolates. The antimicrobial susceptibility patterns were very similar between clones belonging to the same clonal complex, ST81 ^6A and ST282 ^6D ; nonsusceptibilities to penicillin and cefuroxime, high MICs of ceftriaxone, and high resistance rates to trimethoprim-sulfamethoxazole. However, ST3171 ^6D isolates showed resistance to only macrolides and clindamycin. The sequences of 11 genes around the cps locus indicated the same genetic backgrounds between the ST81 ^6A and ST282 ^6D isolates. On the other hand, ST3171 ^6D isolates showed nucleotide and amino acid differences from ST81 ^6A and ST282 ^6D isolates in most genes, indicating a different genetic background. The mosaic structure of dexB gene in ST282 ^6D isolates indicated that recombination might occur in the dexB gene. Our results suggest that the multidrug-resistant ST282 ^6D pneumococcal clone has emerged by serial genetic recombination, including capsular switch.