Objective. We sought to investigate the role of Streptococcus pneumoniae (SP) nasopharyngeal (NP) colonization after successful antibiotic treatment (Rx) of acute otitis media (AOM) in recurrent AOM (RAOM). Patients and methods. NP cultures were obtained from 494 (93%) of 530 patients at the end of antibiotic treatment (EOT). Results. At enrollment, middle ear fluid (MEF) cultures in 418 (79%) of 530 patients were positive for pathogens. At EOT, NP cultures in 208 (42%) of 494 patients were positive for SP. RAOM was found in 130 (26%) of 494 patients: 66 (32%) of 208 with SP-positive NP and 64 of 286 (22%) without SP-positive NP at EOT (P = .026). MEF was positive for SP during RAOM in 34 (61%) of 56 patients with SP-positive NP and 17 (36%) of 47 patients without SP-positive NP at EOT (P = .022). The same serotype was identified in 24 (80%) of 30 SP pairs; complete identity was found between isolates in 22 (96%) of 23 SP pairs. Conclusions. Early RAOM was more commonly caused by SP if the organism was present in NP at EOT during the initial AOM episode. Most SP-RAOM episodes were caused by SP isolates present in NP at EOT during the previous AOM episode.