CTX-M ESBLs have emerged as the predominant type of ESBLs in many parts of the world. However, data about the presence of CTX-M β-lactamases in Cairo University Hospitals are still missing. Our study was carried out to detect the presence of CTX-M ESBL-producers among isolates of Klebsiella spp. and to identify the predominant specific CTX-M group in Cairo University Hospitals, Egypt. Methods: In our study 100 Klebsiella clinical isolates were identified as K. pneumoniae using Microbact TM gram-negative identification system 12A for Enterobacteriaceae (Oxoid, Basingstoke, UK). The isolates were phenotypically confirmed as ESBL producers by both the double disk synergy test (DDST) and combined disk test according to the guidelines of the Clinical and Laboratory Standards Institute, 2010. Further genotypic analysis was done using PCR to amplify a universal DNA fragment specific for the different CTX-M β-lactamases to detect the presence of CTX-M gene followed by RFLP to identify the specific blaCTX-M groups. Results: the CTX-M gene was found in 16 (16%) of the ESBL-producing K. pneumoniae clinical isolates; 14 (87.5%) of them belonged to CTX-M-1-group and 2 (12.5%) belonged to CTX-M-8-group. Sequencing of two randomly selected isolates from the CTX-M-1 group identified blaCTX-M-15 (GenBank accession no. JN849393). In our study 76% of ESBL- producing K. pneumoniae infection were health care-associated, 7.9% of them were CTX-M producers. The rest of the ESBL isolates (24%) were community-acquired infections, 41.7% of them were CTX-M producers p value < 0.001. Thus a significantly higher percent of the CTX-M gene was found among community acquired infections. Conclusion: This demonstrates for the first time the incidence of CTX-M enzymes, the predominant CTX-M group and the presence of CTX-M-15 gene among ESBL-producing Klebsiella pneumoniae in Cairo University Hospitals.