Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) has become a real threat to hospitals worldwide with significant morbidity and mortality. Aim: to determine the rate of CRKP in ICUs of Zagazig University hospitals (ZUHs) by confirmatory phenotypic and molecular methods Subjects and Methods: This prospective cross sectional study included 86 K. pneumoniae isolates from hospitalized patients in ICUs. Carbapenem resistance was identified by VITEK2 COMPACT system and Carbapenemase activities were identified by Modified Hodge Test, (MHT), modified Carbapenem Inactivation Method (mCIM) and KPC/MBL and OXA-48 Confirm Kit (KMOC test). Carbapenemase-encoding genes (blaKPC, blaNDM, blaVIM, blaIMP, and blaOXA48) were detected by Multiplex PCR. Results: 66.3%( 57/86) of K. pneumoniae isolates were CRKP. Hospital acquired infection (HAI) accounts for 84.2% among CRKP isolates.The rate of resistance by MHT, mCIM and KMOC test for carbapenems was 49.1%, 86% and 80.7% for CRKP isolates respectively. The blaNDM-1, blaOXA-48 and blaKPC genes were detected at a rate of 31.6%, 24.6%, and 12.3% by PCR respectively. Coexistence of carbapenemases was detected in 15.7% of isolates. Resistance pattern of Eravacycline, Cefiderocol, Ceftazidime/avibactam and Ceftolozane/tazobactam was 52%, 65%, 82.2% and 98% respectively. Conclusion: CRKP was responsible for a significant number of HAI cases in the ICUs of ZUHs. Antibiotic resistance was shown to be widespread in our study. The identification of carbapenemases classes will be useful for the improvement of patient’s treatment and prognosis and for infections control measures in ICUs.