Purpose: The incidence of carbapenem-resistant Enterobacteriaceae (CRE) has increased in the last two decades, causing significant morbidity and mortality. Our study investigated the factors associated with mortality from CRE bloodstream infection in a single center in Oman. Methods: Data from adult patients with CRE bacteremia, over a 10-year period, were retrospectively collected. Demographic and clinical characteristics were compared according to intensive care unit (ICU) admission status and mortality. A logistic regression model was used to evaluate factors associated with mortality. Results: 169 cases of CRE bacteremia were identified, of whom 93 (55%) required ICU admission and 96 (56.8%) died. Patients who required ICU care were more likely to require organ transplant (15% vs 4.0%; p = 0.02), be on immunosuppressants (31% vs 17%; p = 0.035), be transferred from other hospitals (40% vs 14%; p 0.001), be colonized with CRE (73% vs 43%; p 0.001), have vascular lines (85% vs 42%; p 0.001), be on mechanical ventilation (91% vs 9.2%; p 0.001), require a longer stay (37 vs 17 days; p 0.001), and have increased mortality (80% vs 29%; p 0.001). In the multivariate analysis, mechanical ventilation (adjusted odds ratio (aOR) 15.3; 95% confidence interval 5.39–43.2; p 0.001) and prior use of the broad-spectrum antibiotics meropenem (p = 0.01) and piperacillin/tazobactam (p = 0.026) were associated with CRE mortality. Conclusion: CRE bacteremia carries a high mortality rate in patients requiring ICU care. Implementation of infection control measures and antimicrobial stewardship programs are essential in reducing the rates of CRE BSI.