The potential coverage of antibiotic-resistant pneumococci causing acute otitis media (AOM) by 7-, 9-, and 11-valent conjugate pneumococcal vaccines was studied in southern Israel. A total of 876 cases of pneumococcal AOM were studied in the context of various clinical conditions. Of the isolates, 68% were resistant to >/=1 drug, 61% were resistant to penicillin, and 13% were resistant to >/=3 antibiotic classes. Antibiotic resistance and coverage by the various candidates were age and population dependent and were higher among those with a complicated clinical course, as indicated by recent antibiotic use and recurrence of AOM. The results suggest that, if efficacious, the conjugate pneumococcal vaccines can substantially reduce the occurrence of pneumococcal AOM in general and complicated pneumococcal AOM in particular.