Carbapenem-resistant Organism (CRO) cannot be given a higher priority because there are limited medications available and the rapid replication of the pathogens due to immunosuppression of hematologic malignancy patients. Nevertheless, risk factors and prognosis of CRO infections after chimeric antigen receptor-modified T cells (CAR-T) therapy are still unclear and topical. This study was conducted to analyze the risk factors for CRO infection in patients with hematologic malignancies following CAR-T therapy and the prognosis one year after CAR-T infusion. Patients who were diagnosed with hematologic malignancies and treated with CAR-T therapy between June 2018 and December 2020 at our center were included. The case group (35) consisted of patients who developed CRO infections within 1 year of CAR-T infusion, while the control group (280) consisted of patients who did not develop CRO infections. Shockingly, the therapy failures occurred in 62.82% of CRO patients versus 13.21% of the control group (P =0.000). Patients with CRO colonization (OR=15.48 CI (6.43-37.25) P=0.000) and hypoproteinemia (OR=2.84 CI (1.20-6.73) P=0.018) were susceptible to CRO infections. CRO infections (HR=4.40 CI(2.32-8.37) P=0.000), prophylaxis with combination regimes containing MRSA active agents (HR=5.42 CI(2.65-11.11) P=0.000), and bacterial infections occurring within 30 days of CAR-T infusion (HR=1.97 CI(1.08-3.59) P=0.028) were risk factors for poor outcomes within 1 year. This study shows that prophylaxis of CRO infection should be a top priority in CAR-T therapy, the serum albumin level of the patients should be dynamically monitored and interfered if necessary, and we should be more cautious in prophylaxis with anti-MRSA activity agents.Copyright © 2023. Published by Elsevier Ltd.