This study aimed to compare the clonal distribution of common pneumococcal strains not included in the 7-valent pneumococcal conjugate vaccine (PCV7) that were isolated from cases of acute otitis media (AOM) and invasive pneumococcal disease (IPD) in two distinct ethnic populations in southern Israel during the decade (1999 to 2008) preceding PCV7 implementation. Isolates recovered from Jewish and Bedouin children <5 years old were characterized by antibiotic resistance and molecular epidemiology using pulsed-field gel electrophoresis and multilocus sequence typing. Of 5,236 AOM and 425 IPD isolates, 43% and 57% were from Jewish and Bedouin children, respectively. PCV7 accounted for 54% and 45% of the AOM and IPD episodes, respectively. Eleven major non-PCV7 serotypes (1, 3, 5, 6A, 7F, 12F, 15B/C, 19A, 21, 33F, and 35B) constituted 31% and 42% of the AOM and IPD episodes, respectively. The clonal distributions of the 11 non-PCV7 serotypes and their antibiotic susceptibilities were significantly different among the two ethnic populations in both the AOM and IPD groups. About half of the AOM and IPD cases resulted from non-PCV7 pneumococci, even before PCV7 implementation. The significant differences between the two ethnic populations suggest that lifestyle and microenvironment are major determinants in the clonal distribution of disease-causing pneumococci. Post-PCV7 surveillance is important in understanding non-PCV7 clonal expansion in the two distinct populations.