AbstractWe performed whole-genome sequencing of three multidrug-resistant KPC-producing Klebsiella pneumoniae isolates recovered from patients in a tertiary-care hospital in Abu Dhabi, UAE, and conducted a comparative genomic analysis with previously reported blaKPC−2-positive isolates from the region. The study aimed to characterize acquired antimicrobial resistance genes (ARGs), assess their phylogenetic context, and analyze the plasmids carrying blaKPC−2. Between 2017 and 2018, 162 carbapenem-resistant K. pneumoniae (CRKP) isolates were collected from four tertiary care hospitals in Abu Dhabi. Antibiotic susceptibility was determined using the Vitek2 system, and PCR was used to detect carbapenemase genes. Whole-genome sequencing was performed for the three blaKPC-2-positive isolates using Illumina NovaSeq, and assemblies were generated with SPAdes 3.9. PlasmidSPAdes and PLACNETw were used to reconstruct blaKPC-2-carrying plasmids, which were then compared with plasmids described in earlier UAE reports. The three K. pneumoniae isolates belonged to sequence types ST11, ST20, and ST231, respectively. All harbored the blaKPC−2 gene on IncFII-type plasmids of varying sizes. Our comparative analysis demonstrated variability in the genetic platforms carrying blaKPC−2, with two transposons (Tn1721a and Tn4401b) identified as the main structures associated with this gene in UAE isolates. Conclusions: Our findings highlight the diversity of genetic platforms carrying blaKPC-2 in the UAE, particularly the frequent association with IncFII plasmids and their potential role in the dissemination of antimicrobial resistance. Although blaKPC-2 is a globally widespread carbapenemase gene, it has been rarely reported in the United Arab Emirates (UAE). To date, only two studies describing blaKPC-2-carrying Klebsiella pneumoniae isolates have been published from the region—in 2015 and 2019. Our study presents a comprehensive genomic analysis of blaKPC-2-positive isolates collected in 2017–2018 from tertiary care hospitals in the UAE. Compared to previous reports, this study employed advanced bioinformatics tools and conducted deep genomic surveillance, including resistome, plasmidome, transposon mapping, and phylogenetic comparisons with public genomes. We identified distinct genetic platforms carrying blaKPC-2, notably the association with IncFII plasmids and the continued presence of the Tn4401b transposon. Although blaKPC-2 is present in the UAE, it remains underreported, likely due to limited regional sequencing efforts. This study provides essential baseline genomic data and a comparative framework to support ongoing and future surveillance of antimicrobial resistance in the Gulf region.