Background <p>Rising antimicrobial resistance (AMR) is an acute public health emergency impeding the clinical efficacy of surgical interventions. Biliary stent placement is one of the routine surgical procedures that rarely lead to infections that are empirically managed by broad-spectrum β-lactams and fluoroquinolones. Critical priority pathogens, such as carbapenem-resistant <i>Escherichia coli</i> challenge treatment outcomes and infection prevention.</p> Methods and results <p>Two carbapenem-resistant <i>Escherichia coli</i> isolates recovered from biliary stent-infected patients were investigated for drug resistance and molecular typing from a tertiary-care hospital in eastern India. The isolates were extensively drug-resistant (XDR) and remained susceptible to aminoglycosides, tigecycline, fosfomycin, or colistin. Carbapenemase <i>bla</i>_NDM-5 was carried by both the isolates that either belonged to strain type ST361 or ST405.</p> Conclusions <p>This is the first report of carbapenem-resistant <i>Escherichia coli</i> carrying <i>bla</i>_NDM-5 being recovered from biliary stent infections in India. Targeted antibiotic therapy is pivotal for the XDR infections, while molecular typing facilitates infection prevention measures by source tracking and control.</p>