Objective To investigate clearly the causes, characteristics and patterns of the clustered epidemic of tuberculosis in this high school and provide scientific basis for improving continuously implementation of tuberculosis control strategies in schools. Methods Complying with the specific requirements of Shantou Health Bureau of Guangdong Province on handling this affair, close contacts who were deemed to be in close contact with index case in terms of study, living space and interpersonal interaction were screened. Suspicious symptom examination, chest x-ray examination and skin test of tuberculin (PPD) were performed among these close contacts. For diagnosing comprehensively to tuberculosis, interferon gamma release assay (IGRA), CT image examination, sputum smear acid-fast staining microscopic examination, isolation and species identification of mycobacteria and Xpert MTB/RIF molecular detection were performed for any patients with any abnormal results from the above- mentioned screening process. In order that the transmission relationships were established correctly bases on genic cluster patterns of MIRU - VNTR, 15 - loci MIRU - VNTR (ETRA, ETRB, ETRC, ETRE, ETRF, MIRU10, MIRU20, MIRU26, MIRU39, MIRU40, Mtub04, Mtub21, Mtub38, Oub11b, and Qub26) of Mycobacterium tuberculosis from cases with tuberculosis were detected and analyzed. Results The first, the index case had presented these lesions such as patchy, speckled and streak -like increased density images in the upper lobe of both lungs and multiple cavities of which the largest was about 2.1 cm × 1.7 cm in the upper lobe of left lung, and his laboratorial results of isolation and molecular detection of pathogen were positive. The second, 15 other cases with pulmonary tuberculosis were found following three months after the discovery of the index case in this school. Among these cases, there were clinical symptoms in 3 cases, sputum-smear suspicious positive in 3 cases, pathogen isolation culture positive in 9 cases and molecular detection positive in 7 cases respectively. As to close contact with index case, 10 cases had close spatial contact clouding the same classroom, dormitory or evening self-study classroom and 4 cases direct or indirect interpersonal contact while one case had no clear clues of close contact. The third, genotyping laboratory results demonstrated that the copy number patterns of 15-loci MIRU -VNTR were identical in eight isolates among nine isolates, of which one isolate was not obtained genotyping result. Finally, assuming “PPD skin test ≥ 5 mm” was regard as the criterion of latent tuberculosis infection, 252 out of 409 patients were positive and the latent infection rate was 61.61%.There was a significant difference in latent infection rate between the students from class of the index case and the students from classes of other cases (100% vs. 56.58%, χ² = 30.781, P < 0.001). However, there is no significant difference between the following population groups: male vs.female, resident students vs.day students, students from different floors and students from the same side of same vs.students from the opposite side of same (P > 0.05). Conclusions This clustered epidemic of tuberculosis was caused by the same infectious source, which caused much higher latent tuberculosis infection rate than that of the general population.It is urgent to strengthen the effective implementation of school tuberculosis control measures because the main reason causing this affair is serious lack of management of school tuberculosis control. [ABSTRACT FROM AUTHOR]