Introduction: Streptococcus pyogenes infection causes a wide spectrum of clinical manifestations. Invasive disease (ID) is defined by the isolation of the microorganism from sterile sites. Objective: To analyze the clinical, epidemiological and molecular characteristics of ID by S.pyogenes in children hospitalized at Pediatric Hospital Pereira Rossell, from January 2005 to January 2013. Materials and Methods: A descriptive retrospective study was done in cases with isolation of S.pyogenes from sterile sites. Epidemiological variables, disease characteristics, laboratory parameters, treatment regimen received, hospitalization days and clinical outcome were analyzed. The presence of 4 genes encoding for virulence factors and chromosome profile studied by pulsed-field electrophoresis were done in the isolated strains. Results: A total of 42 cases (rate: 4.6 out of 10,000 admissions) were detected, from which 32 were analyzed. Average age was 44.7 months (14/32 < 2 years of age). In 5 cases, the portal of entry was identified. Clinical presentations were: osteoarticular infections (n = 15), shock (n = 6), skin and soft-tissue infections (n = 5), pneumonia (n = 3) and bacteremias (n = 3). Twenty cases required surgical procedures and 13 required intensive care admission. Average hospital stay was 17 days and one patient died. Molecular studies were performed in five strains; 4 different toxin profiles and pulsotypes were identified. Discussion: The incidence of ID at our hospital is similar to other series in the region. A better knowledge of clinical presentation and its relation with molecular characteristics represents a challenge.