Objective: Extended spectrum β-lactamases (ESBL) producing Enterobacteriaceae predominantly E. coli and K. pneumoniae bacteremia have limited treatment options and high mortality. The objective was to determine the risk factors for in-hospital mortality particularly treatment with Carbapenem versus Beta lactam/beta lactamase combination (BL/BLI) in patients with Ceftriaxone resistant E. coli bacteremia. A retrospective cohort study was conducted at the Aga Khan University, Karachi, Pakistan. Adult patients with sepsis and monomicrobial Ceftriaxone resistant E. coli bacteremia were enrolled. Factors associated with mortality in patients were determined using logistic regression analysis. Results: Mortality rate was 37% in those empirically treated with carbapenem compared to 20% treated with BL/BLI combination therapy (p-value: 0.012) and was 21% in those treated with a carbapenem compared to 13% in patients definitively treated with BL/BLI combination therapy (p-value: 0.152). In multivariable logistic regression analysis, only Pitt bacteremia score of ≥ four was significantly associated with mortality (OR: 7.7 CI: 2.6-22.8) while a urinary source of bacteremia was protective (OR: 0.26 CI: 0.11-0.58). In-hospital mortality in patients with Ceftriaxone resistant E. coli bacteremia did not differ in patients treated with either a carbapenem or BL/BLI combination. However, Pitt bacteremia score of ≥ 4 was strongly associated with mortality.