Whole-genome sequencing (WGS) is a new technology to study the transmission of Mycobacterium tuberculosis (M. tuberculosis), in addition to variable-number tandem-repeat (VNTR) typing and clustering. In this study, a total of 55 XDR-TB strains isolated from a hospital in Chongqing from 2003 to 2009 were genotyped and clustered (≤12 SNPs) by 9＋3 loci VNTR and WGS respectively. The evolutionary trees by the two methods were built, and the consistency and differences in clustering were compared. By VNTR, 55 strains of M. tuberculosis could be divided into 45 genotypes, of which 39 were single genotypes and 16 were in 6 clusters. Twenty of the 55 strains (36.4%) were divided into 5 clusters by WGS. The consistency of the two methods in identifying clusters was 63.6%. Compared with WGS, VNTR typing method had a sensitivity of 40.0% and a specificity of 77.1%. VNTR typing method had a higher specificity than WGS. The results indicate that VNTR typing alone might incorrectly estimate the transmission of XDR-TB, and clustering by no more than 12 SNPs for recent transmission of XDR-TB is a practical standard deserving more studies.