BACKGROUND: Occupational exposure-related risk of Mycobacterium tuberculosis infection has been reported for village doctors in China. This prospective study aims to estimate the infection acquisition in this key population.METHODS: At baseline, all village doctors registered in Zhongmu County were tested by QuantiFERON®-TB Gold In-Tube (QFT) and QuantiFERON®-TB Gold Plus (QFT-Plus) in parallel. Those negatives for either of the tests were retested to identify conversions at the 2-year follow-up investigation.RESULTS: A total of 367 eligible participants completed the 2-year follow-up survey with frequency of conversion of 5.0% (18/361) for QFT and 6.1% (21/343) for QFT-Plus. The agreement of follow-up results between the tests was 93.2% with a κ coefficient of 0.43 (95%CI 0.20-0.65). Among QFT-Plus convertors, the difference between TB1 and TB2 tubes (TB2-TB1) was significantly increased as compared with baseline results (P = 0.039). Participants from the villages with occurrence of microbiologically confirmed pulmonary TB showed higher frequency of QFT conversions (11.0% vs. 3.2%, P = 0.011) and QFT-Plus conversions (12.3% vs. 4.4%, P = 0.027) than those from the villages without occurrence.CONCLUSION: Our results consistently suggest that capability on occupational protection and M. tuberculosis infection control should be improved in village doctors in China.