Abstract: Objective To evaluate the feasibility of preventive therapy for latent Mycobacterium (M.) tuberculosis infection in middle school students, and provide evidence for the development of school tuberculosis (TB) control and prevention strategies. Methods According to local TB epidemic and the current status of school TB control and prevention, three middle school in a county from Shanxi province were selected.A total of 2 822 students were surveyed. PPD was adopted for skin test in the detection oflatent M. tuberculosis infection, the average diameter of induration 15 mm, blisters, necrosis,or lymphatic inflammation were believed to be strongly positive. The chest X-ray, routine blood test, liver and renal functions test were carried out for excluding activity TB. Based on the informed consent, 6 months isoniazid therapy were given, the daily dosage was 10 mg/kg/d, less than 300 mg/d. Results The screening rate was 85.05% (2 400/2 822), the first 3 reasons for refusing screening were history of allergies (47.63%), being ill (19.43%) and fever (17.30%). The strong positive rate was 2.63% (63/2 400). A total of 38 students received preventive therapy, thestudents who refused the treatment were all afraid of adverse drug reaction. All the students who received the treatment completed the courses of therapy and the regular drug taking rate was 100%, and 4 cases of mild adverse reaction occurred. Conclusion Multi-department cooperation, health education and social mobilization were essential to improve the acceptability of preventive therapy for latent M. tuberculosis infection in middle school students. Factors such as local TB epidemic, medical service system, funding, cooperation and so on should be considered for the development of TB prevention strategies.