Abstract: Objective To track the transmission of multidrug-resistant tuberculosis (MDR-TB) based on whole genome sequencing technology.Methods Isolates of 8 MDR-TB patients deemed as a cluster based on VNTR genotypes during 2009 to 2012 were analyzed by whole genome sequencing to describe the transmission of MDR-TB.Results The index case of the cluster was a relapse MDR-TB patient,who transmitted SM-/INH-resistant Mycobacterium tuberculosis to other 7 patients in 3 years.Conclusion Whole genome sequencing can remedy the deficiency of the traditional epidemiology investigation and genotyping technology, and allows accurate description of the direction and details of transmission between TB cases. The technique could identify the index case and predict missing cases, and accurately reveal the transmission route of multidrug-resistant tuberculosis.