A retrospective cohort study was conducted to determine the impact of antimicrobial resistance of Streptococcus pneumoniae and of capsular types on mortality in children under 5 in Colombia. Data were from the Pan American Health Organizations Regional System for Vaccines study of S. pneumoniae serotypes. Severe pneumonia and meningitis caused by S. pneumoniae continue to be associated with high mortality rates. Clinical records of 245 children under 5 treated for invasive disease caused by S. pneumoniae between 1994 and 1996 in hospitals in Bogota Cali and Medellin were analyzed. There were 124 cases of pneumonia 104 of meningitis 8 of peritonitis and 6 of arthritis. 29 of the 245 children died including 13 of the 82 girls (15.9%) and 16 of the 163 boys (9.8%). 20 (19.2%) died of meningitis 8 (6.4%) of pneumonia and 1 (5.9%) of peritonitis. No significant differences between those dying and surviving were found in univariate analysis of age sex underlying disease or concordance of antimicrobial treatment. Variables associated with mortality in the univariate analysis included diagnosis of meningitis; resistance to penicillin trimethoprim-sulfamethoxazole (TMS) or erythromycin; multiresistance; and serotypes 6 23F 7F 8 and 35B. Factors associated with mortality in logistic regression were serotypes 7F (OR = 7.13 P = 0.04) and 8 (OR = 13.8 P = 0.07) meningitis (R = 5.02 P = 0.0001) resistance to TMS (OR = 2.62 P = 0.02) and polypnea (OR = 2.74 P = 0.03). Antimicrobial resistance was the factor most associated with mortality in meningitis patients while serotype was most consistently associated in pneumonia patients.