Introduction: Studies examining carbapenemase producing carbapenem resistant Enterobacterales (CP-CRE) transmission incorporating clinical and genomic data in Indian hospitals are lacking. We investigated the prevalence, risk factors for CP-CRE peri-rectal colonization on admission and acquisition during hospital stay and genomic epidemiology of CP-CRE isolates in an adult surgical intensive care unit (SICU) in a tertiary-care hospital in India. Methods: SICU patients admitted from July 31 to November 30, 2023 were prospectively enrolled. Peri-rectal swabs (PRS) were collected at SICU admission and discharge, and hospital discharge. Environmental sampling of sinks was performed. Swabs were plated on selective agar (CHROMagarTMmSuperCARBATM) for CP-CRE isolation. Whole genome sequencing of CP-CRE isolates was performed to investigate antimicrobial resistance gene (ARG) abundance, strain typing (ST), and relatedness classified by community-associated (CA), healthcare-associated (HCA), hospital-acquired (HA), and environmental isolates. Results: 56 (28%) of 203 enrolled patients were colonized with CP-CRE on SICU admission. Among 147 admission-negative patients, 113 had repeat PRS testing > = 1 times during their stay; 43 (29%; 43/147) acquired CP-CRE (Figure 1). The predominant organism in admission and acquisition cases was Escherichia coli (52%) and Klebsiella pneumoniae (37%), respectively (Figure 2). Previous hospitalization = 2 antibiotics (aOR 2.77; 95%CI 1.12-6.82) were associated with admission CP-CRE colonization (Figure 3). In Cox regression analysis hospital stay before SICU admission was associated with CP-CRE acquisition in the SICU, but no risk factor was associated with acquisition during the entire hospital stay (Figure 4). Abundance of ARGs was lower in CA CP-CRE isolates compared to HCA, HA and environmental isolates (Figure 5). blaNDM and blaOXA genes were present in 79% (99/126) and 29% (36/126) of isolates, respectively; blaNDM-5 was the most common carbapenemase [65 (52%) of 126 isolates] (Figure 6A). E. coli ST410, which was associated with HA and HCA classifications was the most frequent ST (n=17) and 70% (12/17) carried NDM (Figure 6B). Twenty-seven E. coli and 17 K. pneumoniae isolates were separated by 20 or fewer core genome single-nucleotide polymorphisms, indicating potential relatedness amongst CP-CRE (Figure 7). Conclusion: More than 25% of SICU patients were colonized with CP-CRE on admission and also acquired CP-CRE during hospital stay. Healthcare-related CP-CRE isolates carried more resistances genes with NDM being the most commonly detected resistance gene in this cohort. Small sample size limited our understanding of risk factors associated with CP-CRE acquisition in hospital.