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Childhood tuberculosis (TB) is a major infectious disease causing morbidity and mortality in children and yet has been largely ignored until recently. This study is the first study to characterize childhood TB in China incorporating both Mycobacterium tuberculosis genetic characteristics and patient data.We analyzed a total of 331 culture-confirmed childhood TB cases and 158 M. tuberculosis isolates from a subset of the study sample. Univariate and multivariate logistic regression analyses were performed to identify host and microbial predictors for having extrathoracic TB alone, concurrent thoracic and extrathoracic TB and TB meningitis (TBM), respectively.Fifty-eight percent (192/331) of the study subjects had extrathoracic TB, and 139 (42.0%) cases had TBM. Both age of less than 5 years [adjusted odds ratio (OR): 4.52; 95% confidence interval (CI): 1.27–16.16] and female sex (adjusted OR: 2.72; 95% CI: 1.03–7.18) were significantly associated with extrathoracic TB alone, whereas living in rural area (adjusted OR: 2.35; 95% CI: 1.06–5.18) was significantly associated with thoracic–extrathoracic TB. Age of less than 5 years was also strongly associated with TBM (adjusted OR: 3.63; 95% CI: 1.64–8.05). Sixty-four percent (101/158) of the study isolates were Beijing lineage strains. Infection with Beijing lineage strains was significantly associated with thoracic–extrathoracic TB (adjusted OR: 2.39; 95% CI: 1.11–5.15) and TBM (adjusted OR: 2.25; 95% CI: 1.10–4.60).Both microbial and host factors can affect the outcome of M. tuberculosis infection in children. Future studies incorporating host and pathogen data from different populations are warranted to develop new strategies for childhood TB control.