Purpose Streptococcus pneumoniae (S. pneumoniae) is the etiology of severe and life-threatening infections in children less than 5 years old. Though pneumococcal conjugate vaccines (PCVs) are effective in the prevention of pneumococcal infections, yet they are not included in the National Immunization Program in Egypt pending the identification of pathogenic serotypes. As S. pneumoniae colonization of the pharynx predisposes to pneumonia and invasive pneumococcal disease (IPD) caused by the colonizing serotypes, identification of the nasopharyngeal (NP) serotypes can be a surrogate to the invasive serotypes. In this study, we aimed to 1. Identify the serotypes and antimicrobial susceptibility testing (AST) of Streptococcus pneumoniae colonizing the nasopharynx of Egyptian children younger than 5 years in two successive winter seasons. 2. Correlate the identified serotypes with vaccine coverage of the 13-valent conjugate pneumococcal vaccines (PCV13). 3. Compare the serotypes and AST of S. pneumoniae from NP to those of IPD that were routinely identified in our clinical laboratory during the study period. Materials and Methods The study was conducted in two successive winter seasons (December 2015–March 2016; December 2016–March 2017). We enrolled 334 children, aged 6 months to 5 years, attending the outpatient general clinics of Cairo University Children Hospital, excluding those with fever, signs of infection, history of antibiotic intake or hospitalization in the preceding month. We tested NP swabs for S. pneumoniae by culture and real-time PCR. Serotyping was performed by sequential multiplex PCR for all positive samples. AST was done to S. pneumoniae isolates by Vitek-2™ (BioMérieux, Marcy-L’Etoile, France). We included routinely detected S. pneumoniae from sterile body sites during the study period, and identified their serotypes and AST. Results PCR was positive for pneumococci in 217 out of 334 pharyngeal swabs (65%), including 186 typable samples. The most common serotypes were serotypes 1, 6ABC, 19 F, 5 and 18ABC. By culture, we isolated only 110 out of 334 pharyngeal swabs (32.9%). The theoretical coverage of the PCV13 vaccine for the detected serotypes was 77.4%. The AST of NP isolates revealed low susceptibility rates to all antimicrobials except for vancomycin, linezolid, levofloxacin and clindamycin. During the study period, we identified 40 IPD; 21 identified by PCR and 19 by culture. The commonest pneumococcal serotypes were 1, 18ABC, 6ABC and 5. The PCV13 coverage was 75%. By Vitek-2, the isolates showed 100%, 100%, 94.7%, 89.5%, 84.2%, 84.2% and 78.9% susceptibility to vancomycin, linezolid, clindamycin, levofloxacin, penicillin, cefotaxim and erythromycin, respectively. Conclusion Based on the serotype vaccine coverage and the emerging antimicrobial resistance of S. pneumoniae , PCVs will be valuable to Egyptian children.