In this study, we performed an in-depth comparison of genome-sequenced Mycobacterium tuberculosis isolates from Ireland with isolates from other countries. The sequenced isolates from Ireland mostly belonged to Lineage 4 (64.15 %) with Lineages 2 (17.27 %), 1 (13.21 %), 3 (5.22 %), and 5 (0.15 %) also represented. Of these, Lineages 2 (47.57 %) and 4 (34.95 %) accounted for the majority of the isolates that were resistant to at least rifampicin. By performing hierarchical clustering of the genomes, we determined that many drug-resistant (DR) strains of Lineage 2 collected in Ireland belonged to larger international clusters of the bacterium that were dominant in countries that included Estonia, Georgia, Ukraine, and Moldova. Lineage 4 DR-TB strains isolated in Ireland were also commonly part of large international clusters but the major countries differed i.e. Eswatini, Germany, United Kingdom, and Mozambique. Based on single nucleotide polymorphism (SNP) analysis, there was no evidence found of widespread onward transmission of DR-TB isolates in Ireland. This indicates that a key source of DR-TB in Ireland is translocation of M. tuberculosis from countries where specific genetic clusters of drug-resistant strains are prevalent. This study has implications for interpreting future trends in TB drug resistance. As an open economy with extensive international travel connections, Ireland is sensitive to the emergence of resistant isolates of M. tuberculosis elsewhere. In addition to caution being applied with respect to TB presenting in individuals from high multi-drug resistant (MDR) TB burden countries, vigilance is also needed for TB in persons from countries where large phylogenetic clusters of DR-TB occur.