Objective. To determine the epidemiology of invasive pneumococcal disease (IPD) and the antibiotic susceptibility and serotype distribution of S. pneumoniae in pediatric patients in Lima, Peru. Methods. A 2-year, multicenter, passive surveillance study conducted from May 2006- April 2008 in 11 public hospitals and five private laboratories in Lima, Peru, in patients less than 16 years of age with sterile site cultures yielding S. pneumoniae. Antibiotic susceptibility was performed by Etest® (AB Biodisk, Solna, Switzerland). Strains were serotyped by the Quellung reaction. Results. In all, 101 IPD episodes were studied, 68.3% of which were among children less than 24 months of age. Diagnoses were: pneumonia (47.5%), meningitis (38.6%), and sepsis (7.9%). The overall case fatality rate was 22.0%; case fatality rate in meningitis was 32.4%. While 80.0% of fatal cases were in those less than 24 months of age, only 50.7% of non-fatal cases (P < 0.05) were in this age group. Resistance rates were high for trimethoprim/ sulfamethoxazole (76.2%), erythromycin (24.8%), and penicillin (22.8%). The most common serotypes were 14, 6B, 19F, 23F, and 5, which accounted for 69.7% of all strains and 87.0% of penicillin non-susceptible strains. Conclusion. IPD in hospitalized children in Lima is associated with high antimicrobial resistance levels and elevated case fatality rate, especially in young children. This baseline data will be useful for evaluating the effects of vaccine introduction.