Background: Streptococcus pyogenes is one of the major public health concerns causing human infections ranging from skin and throat infections to acute rheumatic fever and post streptococcal glomerulonephritis. Moreover, nowadays drug-resistant strains of S. pyogenes are emerging and can be transmitted through apparently healthy carriers to susceptible individuals. Objective: To assess the prevalence, antimicrobial susceptibility pattern and associated factors S. pyogenes among apparently healthy school children in Mekelle city primary schools, Northern Ethiopia. Methods: A cross-sectional study was conducted among 504 apparently healthy school children from February to May 2018. We used structured questionnaire to collect socio-demographic data. Throat specimens were collected using sterile cotton Swab and transported for culture, antimicrobial susceptibility and identification of S. pyogenes according to standard operating procedures. Data were analyzed using Stata 13 for descriptive statistics, bivariate and multivariate logistic regression. P-value