Background <p>Previous studies analyzing differences in mortality associated with carbapenemase type in patients with a variety of infections caused by carbapenemase-producing <i>Enterobacterales</i> (CPE) have produced conflicting results.</p> Methods <p>We performed a multinational multicenter retrospective cohort study. Adult patients with blood-stream infections (BSI) caused by CPE between 2015 and 2020 were included. The primary outcome was 14-day mortality; 28-day mortality and microbiological failure were secondary outcomes. Clinical and microbiological data were collected and analyzed using conditional logistic regression.</p> Results <p>A total of 360 patients were identified of whom 226 had infections caused by KPC-producing isolates, 109 by NDM-producing isolates and 25 by other carbapenemases. Definitive therapy was colistin-based in 35.1% of patients, ceftazidime/avibactam ± aztreonam (CAZ/AVI ± A) in 28.2% and other in 23.4%. Overall 14-day mortality was 28.1%; carbapenemase type was unassociated with mortality in univariate or multivariate analyses. Antimicrobial therapy was significantly associated with 14-day mortality: patients treated with CAZ/AVI ± A had an adjusted hazard ratio of 0.172 (95% confidence interval 0.063–0.473) for death as compared to patients treated with colistin-based therapy. At 28 days, overall mortality was 35.3%; no association was observed between carbapenemase type and 28-day mortality or microbiological failure.</p> Conclusion <p>After controlling for antimicrobial therapy, we did not find evidence of an association between carbapenemase type and mortality. Ceftazidime/avibactam was associated with a greater than 80% reduction in mortality as compared with colistin.</p>