The purpose of this study was to determine the prevalence of acquired antimicrobial resistance in Streptococcus pneumoniae isolated from nasopharyngeal swabs and blood and cerebrospinal fluid (CSF) specimens of 3,028 children hospitalized with signs or symptoms of pneumonia, sepsis, or meningitis in rural Philippines between 1994 and 2000. Pneumococci were identified using standard methods, serotyped, and their susceptibility to oxacillin, erythromycin, tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole was determined using the disk diffusion method. Penicillin minimum inhibitory concentrations (MICs) of the oxacillin-resistant isolates were further tested. The clonality of the penicillin-nonsusceptible (PNSP) isolates was analyzed using pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Altogether 1,048 isolates were analyzed, of which 35 were invasive and 1,013 nasopharyngeal isolates. None was resistant, but 22 (2.1%) were intermediately resistant to penicillin, 4 (0.2%) were resistant to chloramphenicol, 3 (0.2%) to erythromycin, 39 (3.7%) to tetracycline, and 4 (0.2%) to trimethoprim/sulfamethoxazole. Twelve of the 22 PNSP isolates were of serotype 14 and of sequence type 63. These included the two invasive PNSP isolates. PFGE profiling further identified three separate clusters among the sequence of type 63, serotype 14 (ST63(14)) isolates. Antimicrobial resistance in both invasive and nasopharyngeal pneumococcal pediatric isolates in rural Philippines is rare. In spite of this remote setting, the PNSP isolates of the serotype 14 clusters were of ST63 type, which has been described previously on other continents.