To investigate the molecular epidemiology of pneumococcal nasopharyngeal carriage in Hanoi, Vietnam, we studied 84 pneumococcal strains retrieved from children with upper respiratory tract infections. Serotypes 23F (32%), 19F (21%), 6B (13%), and 14 (10%) were found most often. A significant number of strains were antibiotic resistant. Fifty-two percent of the strains were (intermediate) resistant to penicillin, 87% were (intermediate) resistant to co-trimoxazole, 76% were resistant to tetracycline, 73% were resistant to erythromycin, and 39% were (intermediate) resistant to cefotaxime. Seventy-five percent were resistant to three or more classes of antibiotics. A high degree of genetic heterogeneity among the penicillin resistance genes was observed. In addition, the tetracycline resistance gene tet(M) and the erythromycin resistance gene erm(B) were predominantly observed among the isolates. Molecular analysis of the 84 isolates by restriction fragment end labeling (RFEL) revealed 35 distinct genotypes. Twelve of these genotypes represented a total of eight genetic clusters with 61 isolates (73%). The two largest clusters contained 24 and 12 isolates, and the isolates in those clusters were identical to the two internationally spreading multidrug-resistant clones Spain 23F-1 and Taiwan 19F-14, respectively. The remaining RFEL types were Vietnam specific, as they did not match the types in our reference collection of 193 distinct RFEL types from 16 countries. Furthermore, 57 of the 61 horizontally spreading isolates (93%) in the eight genetic clusters were covered by the seven-valent conjugate vaccine, whereas this vaccine covered only 43% of the isolates with unique genotypes. According to the serotype distribution of the nasopharyngeal pneumococcal isolates, this study suggests a high potential benefit of the seven-valent pneumococcal conjugate vaccine for children in Hanoi.