In 2012, it was estimated that one third of the world population was infected with Mycobacterium tuberculosis (M. tuberculosis) and approximately 8.6 million new cases of tuberculosis (TB) were diagnosed. In Oman, there was a remarkable decrease in TB incidence following the implementation of the National Tuberculosis Control Program in 1981. However, over the past 8 years, the incidence of TB declined slowly with 13 per 100,000 populations in 2012. Aim: The study tested the hypothesis that the sustained influx of expatriates from high risk countries may have prevent TB control program in Oman to reach a proposed elimination target of 1 smear positive per 100,000 population by 2015. The present study used high discriminatory molecular markers (spoligotyping and mycobacterial interspersed repetitive units) to assess transmission patterns and population structure of 540 M. tuberculosis isolates obtained from Omanis and expatriates patients. Results: M. tuberculosis population in Oman was found to be highly diverse. Spoligotyping revealed a total of 257 spoligotype patterns. The predominant spoligotyping families EAI (20%), CAS (20%), LAM (7%), T (7%), Bejing (5%) and Haarlem families (2.6%) were shared between Omanis and expatriates. Also, high level of diversity was observed for most of the examined MIRUS (average h= 0.59), the diversity of all loci was stable between 2008 and 2013. Similar diversity of the examined MIRUs was seen among M. tuberculosis isolates obtained from Omanis (average h = 0.59) and expatriates (average h= 0.59). In addition, the average allelic diversity for all examined MIRU was high for M. tuberculosis isolates obtained from different governorates of Oman. M. tuberculosis isolates with shared spoligotype families were found to be highly diverse when examined by the 17 MIRUs, each isolate carrying distinct MIRU profile. This suggests absence of ongoing transmission between the two groups. There was close genetic relationship between all examined isolates. There was no significant difference in the genetic structure of M. tuberculosis isolates in different years (2008 to 2013) (average Fst =0.02), as well as among Omanis and expatriates (average Fst = 0.0003). Similarly, no genetic differentiation of M. tuberculosis was noted in different governorates in Oman (average Fs: =0.002). Conclusion: The population of M. tuberculosis in Oman is highly diverse but genetically related. The high genetic diversity of M. tuberculosis isolates could be due to reactivation of latent infection or due to imported cases through immigration. So, to decrease the incidence of TB in Oman, it is important to detect people with latent TB infection.