Introduction: The spread of carbapenem-resistant Enterobacterales in hospitals constitutes an important epidemiological and therapeutic problem that especially affects vulnerable patients such as perioperative patients. Materials and Methods: We conducted a descriptive, observational, retrospective case-control study of patients infected with carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE) and carbapenem-sensitive Enterobacterales during the perioperative period in a single-institution. Results: Metallo-beta-lactamase was detected in all the 124 CRE isolates, with NDM-type carbapenemase being dominant, while three isolates coproduced KPC-type enzyme. Steroid use (OR: 3.22, p＜0.01), prior use of two or more antibiotics (OR: 4.04, p=0.01), prior use of broad-spectrum cephalosporins (OR: 2.40, p=0.04) and prior use of carbapenem (OR: 4.77, p=0.03) were the independent risk factors for progressing to CP-CRE infection. Bloodstream infections and pneumonia associated with CP-CRE had higher mortality risk. However, colistin-based combination therapy was not found to reduce the mortality risk for CP-CRE infection during hospitalization compared to patients treated by tigecycline- or fosfomycin-based regimens. Conclusion: High mortality is associated with nosocomial infections in the perioperative period caused by NDM carbapenemase-producing Enterobacterales, of which the dissemination in health care settings in Cuba is a public health challenge.