['To investigate the association between mycobacterial genotype and disease phenotype in children.', 'We describe hospitalised children diagnosed with culture-confirmed tuberculosis (TB) in South Africa, a high TB burden setting. Disease phenotype was classified as intrathoracic or extrathoracic based on mycobacterial culture site. Mycobacterial genotyping was completed using spoligotyping.', 'We analysed 421 isolates from 392 children (median age 2 years, range 0.1-12). Intrathoracic disease was present in 294 (75%) children and extrathoracic disease in 98 (25%). The Beijing genotype was the most prevalent (32.9%), followed by the Latin American Mediterranean (LAM, 28.8%), and S genotypes (6.4%). Age was significantly associated with genotype. Children with the Beijing (OR = 2.36, 95%CI 1.21- 4.60) and S genotypes (OR = 3.47, 95%CI 1.26-9.56) were more likely to have extrathoracic disease compared to children infected with the LAM genotype, in analyses adjusted for age and drug resistance.'] Is mycobacterial genotype associated with disease phenotype in children?