We monitored Streptococcus pneumoniae serotypes causing invasive infections in patients admitted to one hospital in southern Chile during a 10-year period (1994 to 2004). All specimens isolated from patients with invasive S. pneumoniae infections were serotyped at the CDC in Atlanta, GA. A total of 508 isolates belonged to 58 serotypes. There were 95 infections in patients <2 years old, 33 infections in patients 2 to 4 years old, 61 infections in patients 5 to 14 years old, 66 infections in patients 15 to 44 years old, 134 infections in patients 45 to 64 years old, and 120 infections in patients >or=65 years old. The 10 serotypes isolated with the highest frequency in all groups were, in decreasing order, 1, 3, 14, 5, 19F, 6B, 7F, 12F, 23F, and 6A. The 10 most frequent isolates in children under 2 years of age were 1, 6B, 14, 19F, 5, 23F, 6A, 9V, and 7F. In patients >or=65 years old, the most common serotypes were 3, 7F, 1, 14, 19A, 23F, 19F, 35B, 4, and 5. Penicillin resistance was detected in 14 (2.7%) clinical specimens isolated since 1998, with 13 resistant strains identified since 2001. Vaccine coverage for the 7-valent conjugate vaccine was 42% for children <2 years of age. This study is important for the design of vaccines for this region and to evaluate public health measures to decrease pneumococcal infections.